1	Overview of the human vaccine market

1.1	Overview of the vaccine industry background

1.2	Classification of vaccines by technical route

1.3	Overview of the Global Vaccine Market

1.4	Overview of the China Vaccine Market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

Introduction to the definition and mechanism of action of vacines

Source: WHO, Frost & Sulivan analysis

•Vacines contain agents that resemble a disease-causing microrganism, and work by mimicking disease agents and

stimulating the imune system to produce specific humoral imunity and (or) celular imune response.

•The vacine agents trigering the imune system represent antigen and lead to production of T-lymphocytes and

antibodies. Antibodies bind to coresponding antigens and induced cel destruction by other imune cels.

•Vacination is to artificialy input imunogens or imune efector substances into the body, so that the body can

acquire the ability to prevent certain infectious diseases through artificial automatic imunity or artificial pasive

imunity, which belongs to primary prevention.

•Vacination can prevent related diseases, which is an important ways of prevention.

Description

•Inactivated influenza virus often enters human body through injections.

Other methods such as skin patches, aerosols via inhalation devices, and

eating geneticaly enginered plants are also being developed.

Vacine Delivery

Production of

Antibodies

•Vacines use weakened or kiled forms pathogens to ensure that pathogens

don’t develop into the ful blown disease, but just like a disease, they triger

an imune response that creates antibodies.

Pathogen

Exposure

•The goal of imunization is to produce memory of the vacine antigen via a

large population of memory cels. If the real pathogen enters the body in the

future, memory cels wil recognize it.

Protection

•When the familiar antigens are detected, the imune system wil produce

antibodies to atack them. Antibodies produced after imunization with viral

vacines are efective at preventing viral disease.

Overview of the Circulation of Clas I Vacines in China

Source: Frost & Sulivan Analysis

R&D/Biotech Companies

Vacine Manufacturer

POVs

Clas I

Vacines

(Out-of-pocket money)

District/County

CDC

Provincial

CDC

Delivery

Placing

order

Biding &

Procurement

through Provincial

Public Tender

Platform

Distribution

SetlementSetlementPayment

Vacination

Circulation

proces

Fund Flow

1	Overview of the human vaccine market

1.1	Overview of the vaccine industry background

1.2	Classification of vaccines by technical route

1.3	Overview of the Global Vaccine Market

1.4	Overview of the China Vaccine Market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

Recombinant

protein

Vacine

•Introduce the target antigen gene into an expresion vector, and then

transfect it into insect cels, bacteria, yeast, or mamalian cels to

expres a large amount of antigen protein under certain induction

conditions.

•Recombinant subunit vacine

•Virus particle like vacine

•Nanoparticle vacine

Main Vacine Types

•Vacineisabiologicalpreparationthatprovidesactiveacquiredimunityagainstoneorseveraldiseases.Avacine

typicalycontainsasubstancethatresemblesadisease-causingmicrorganismandisoftenmadefromweakenedor

kiledformsofthemicrobe,itstoxins,oroneofitsurfaceproteins.

•Thesubstancestimulatestheproductionofantibodiestorecognizeandestroyanyofthemicrorganismsasociated

withthatsubstancethatitmayencounterinthefuture.

•Curently,vacinescanbedividedintopreventivevacinesandtherapeuticvacines.Therapeuticvacinesarestilin

thestageofresearch,sincethereisnocomercialproductaproved.

CategoryDesign Principle

Inactivated

Vacine

•Inactivated vacines are vacines that use heat or chemical reagents to

kil pathogenic microrganisms, causing them to lose their pathogenic

ability but retain their antigenic properties. They typicaly require large

doses and multiple doses of vacination.

•Whole virion inactivated vacine

•Split vacine

•Inactivated subunit vacine

Viral vector

Vacine

•Constructing genes encoding antigen proteins onto harmles viral

vectors, stably expresing antigen substances in the human body and

inducing specific imune responses

•Adenovirus vector vacine

•Slow virus vector vacine

•Adeno asociated virus vector vacine

Live

atenuated

Vacine

•Atenuated live vacines contain pathogens that have ben artificialy

screned for virulence and have reduced virulence. They do not have

pathogenicity, but stil retain imunogenicity and proliferation ability

•Influenza atenuated live vacine

•Measles atenuated live vacine

•Varicela Vacine

Nucleic acid

Vacine

•Nucleic acid vacines involve directly introducing exogenous genes

(DNA or RNA) encoding a certain antigen protein into animal cels, and

synthesizing the antigen protein through the host cel expresion system.

•DNA vacine

•mRNA vacine

•Circular RNA vacine

Source: Frost & Sulivan

Introduction to vacine types and design principles

Definition and Clasification of Inactivated Subunit Vacines

•Though both inactivated and recombinant subunit vacines contain only pathogen-specific antigens, their production difers

significantly. Inactivated subunit vacines purify antigens directly from live pathogens, while recombinant subunit vacines obtain

them via genetic enginering and expresion systems.

•Unlike whole-pathogen vacines, inactivated subunit vacines contain only specific components from harmful bacteria, parasites, or

viruses. These purified components, caled antigens, are proteins or synthetic peptides and are clasified as protein, polysacharide,

or conjugate subunit vacines, based on the antigen type.

•In1981,Heptavax-B,developedbyHileman,becamethefirstFDA-aprovedinactivatedsubunitvacineforhepatitisB.Itwas

derivedfromhumanblodandcontainedthehepatitisBvirusurfaceantigen,HBsAg.

Technique

Vacine type

Ingredients

Protein Subunit

Vacine

Polysacharide

Subunit Vacine

Relevant

Products

The pathogen is cultured

and the target antigenicpr-

otein is obtained by inacti-

vation, lysis and purification.

Fermentation culture in a

bioreactor, folowed by ba-

cterial lysis to extract and

purify cel wal polysacha-

rides.

Contains specific isolated pro-

teins from viral or bacterial pa-

thogens.

Contains polysacharide com-

ponents found in the cel wals

of some bacteria.

Influenza virus subunit va-

cine containshaemaglutinin

and neuraminidase

Pneumococal polysac-

charide vacine contains po-

docarbophilic polysacharide

SubunitConjugate

Vacine

Cultivation of pathogenic

bacteria, extraction and pu-

rification of polysacharides

and proteins, chemical ac-

tivation, and in vitro cros-

linking.

Clasification of Inactivated Subunit Vacine

Contains polysacharide cha-

ins conjugated to carier pro-

teins

Meningococal ACWY con-

jugate vacinecontains poly-

sacharide conjugated to diph-

theria or tetanus toxoid

Sources: GAVI, Frost & Sulivan

Technical Challenges of
Inactivated Subunit Vaccines

No authoritative or definitive	com	parative conclusion

Comparison Betwen Inactivated Subunit Vacines and Split

Vacines and Analysis of Technical Dificulties

•Inactivated subunit vacines have the advantage of being technicaly mature, safe and with few side efects. In order to

improve imunogenicity, posible methods include the adition of suitable adjuvants and the optimisation of the vacine

proces to improve antigen purity.

Technical

Principle

灭活疫苗

Type

Inactivated Subunit Vacine Versus Split Vacine

Imunogenicity

Inactivated subunit and splitvirion vacines are both derived from inactivated

pathogens, such as influenza virus lysed and subunit vacines, but diferences in

their components lead to distinct characteristics.

Influenza Virus Split

Vacine

Influenza Virus

sSubunit Vacine

Safety

Adition of a lysing agent

to the inactivated virus to

cleave the viral envelope

and release the outer en-

velope proteins as wel as

the iner nuclear and ma-

trix proteins.

Further purification based

on lysed vacine, including

only the main targets of

anti-influenza neutralising

antibodies, haemaglutinin

and neuraminidase.

Enhancing the imunogenicity

•Adjuvants non-specificaly enhance or

modify the imune response to a specific

antigen, bosting its imunogenicity or

altering the response type without being

imunogenic themselves. Due to the weak

imunogenicity of inactivated subunit

vacines, adjuvants are often aded to

improve eficacy.

•Optimizing the vacine production proces

to remove lysing agents, ovalbumin, and

inactivators enhances antigen purity,

bosting both imunogenicity and safety.

Selecting Combinations

•Inactivated subunit vacines contain only

pathogen-specific components as antigens,

so chosing suitable antigens and ensuring

they can induce a suficient imune

response are key chalenges in inactivated

subunit vacine development.

The safety is inferior to

that of inactivated sub-

unit vacines

Single component, high

safety

Source: Frost & Sulivan

Production Proces of Inactivated Subunit Vacines

•An inactivated subunit vacine contains only specific antigens derived from inactivated pathogens through proceses like

lysis and purification. Key production steps include pathogen cultivation, clarification, inactivation, concentration, lysis,

centrifugalpurification, blending,sterile filtration, filing, and quality control.

Pathogen

Cultivation

Harvesting

Viral Fluid

Centrifugal

Purification

ClarificationInactivation

Ultrafiltration and

Concentration

Lysis

Blending

Sterile FiltrationFiling and Quality ControlVacine Product

Source: Frost & Sulivan

Aplications and Clasification of mRNA Vacines

•ThemRNAvacineisanewtypethatusesmRNAsequencesencodingspecificantigens,whichenterhostcelsto

exprestheseantigens,providingpreventionortreatment.

•Itsmainaplicationsincludepreventinginfectiousdiseasesandtreatingtumors,withcurentresearchfocusingon

COVID-19,influenza,RSV,melanoma,prostatecancer,andcolorectalcancer.

•mRNAvacinesareclasifiedasnon-replicatingorself-amplifyingbasedonthemRNAtype.

•InAugust2021,PfizerandBioNTech’sBNT162b2becametheworld’sfirstaprovedmRNAvacine.

Clasification of mRNA Vacines

Non-replicating mRNA Vacine

Self-amplifying mRNVacine

Aplication Areas of mRNA Vacines

Antigen

Sequence

(A)n 3’5’ m

G-p-N

3’ UTR5’ UTR

cap structure

Antigen

Sequence

(A)n 3’5’ m

G-p-N

3’ UTR5’ UTR

cap structure

nsP1nsP3

nsP2nsP4

subgenomic promoter

Self-amplifyingmRNAislongerthanon-amplifyingmRNA.Inaditionto

thebasicelementsofmRNA,itincludesanopenreadingframeathe5′

endthatencodesfournonstructuralproteins(nsP1-4)andasubgenomic

promoter.Self-amplifyingmRNAcanreplicatewithinthebody,producing

highlevelsofantigenandinducingastrongerimuneresponse.

mRNA encoding tumor-

specific antigens is de-

livered into the body,

where these antigens

are translated and pre-

sented on cel surfaces,

activating the imune

system to specificaly

recognize and kil tumor

cels.

mRNA vacines for in-

fectious diseases en-

code pathogen

antigens, which, once

expresed in the body,

induce ce-lular and

humoral im-munity,

stimulating anti-bodies

and imune ce-ls to

prevent the pa-thogen.

Infectious DiseasesTumor

Including melanoma,

prostate cancer, lung

cancer, colorectal can-

cer, and others.

Including COVID-19, in-

fluenza, respiratory syn-

cytial virus (RSV) infec-

tion, HIV, and others.

Source: Literature Review, Frost & Sulivan

The Advantages of mRNA Vaccines
Safety: mRNA is a non-infectious, non-integrating platform, eliminating infection and mutagenesis risks. It is biodegradable, and its half-life can be adjusted through modi-fications and delivery methods. Efficacy:Modifications improve mRNA stability and translation. Encapsulation in carrier molecules enables rapid uptake and expression in the cytoplasm, enhancing in vivo delivery. Co- administration with adjuvants boosts immunogenicity. High Production Efficiency: mRNA is produced via in vitro transcription, allowing faster production with a relatively simple process compared to traditional live-attenuated or inactivated virus vaccines. Rapid Response:mRNA vaccines have short development cycles, with easily modifiable sequences, enabling quick responses to emerging infectious diseases.

The Advantages of mRNA Vaccines

Safety: mRNA is a non-infectious, non-integrating platform, eliminating infection and mutagenesis risks. It is biodegradable, and its half-life can be adjusted through modi-fications and delivery methods. Efficacy:Modifications improve mRNA stability and translation. Encapsulation in carrier molecules enables rapid uptake and expression in the cytoplasm, enhancing in vivo delivery. Co- administration with adjuvants boosts immunogenicity. High Production Efficiency: mRNA is produced via in vitro transcription, allowing faster production with a relatively simple process compared to traditional live-attenuated or inactivated virus vaccines. Rapid Response:mRNA vaccines have short development cycles, with easily modifiable sequences, enabling quick responses to emerging infectious diseases.

Challenges to mRNA Vaccines
• mRNA vaccines are less stable, easily degraded, and have a large molecular mass and negative charge, making cell entry difficult and requiring delivery systems. • mRNA vaccineshave a short history of application and lack long-term safety and efficacy data.

Analysis of the mRNA Vacine Production Proces, Advantages,

and Chalenges

•Duetodiferencesinmechanismsandesign,mRNAvacinesofermanyadvantagesovertraditionalvacines,includinghigh

safety,efectivenes,productioneficiency,andrapidresponsecapability.

•TheCOVID-19pandemicaceleratedtheclinicaluseofmRNAvacines.However,despitetheseadvantages,theshortusage

historymeansthatfurtheresearchisnededtoasesthelong-termsafetyandeficacyofmRNAvacines,andchalengesremain

inthedesignofefectivedeliverysystems.

mRNA Vacine Production Proces

Target

Identification

mRNA Sequence

Determination

Plasmid Extraction

and Purification

mRNA

Purification

Plasmid

Linearization

Plasmid Construction

and Amplification

In Vitro Transcription

into mRNA

Delivery

System

mRNA Vacine

Source: Literature Review, Frost & Sulivan

Delivery System	Delivery Mechanism	Advantages	Limitations
Lipid Carrier	• Lipid mixtures with cationic or ionizable lipids form positively charged vesicles that encapsulate negatively charged mRNA. Once inside the cell, the lipid carrier enters an acidic endosome, where the lipids interact with the endosomal membrane, disrupting it and releasing mRNA into the cytoplasm for ribosomal translation.	• Biocompatible • Lowimmunogenicity • Low toxicity	• The molecular shape of lipids may affect mRNA expression efficiency. • The weakly acidic head of ionizable lipids can lead to LNP instability.
Polymer Carriers	• Positively charged cationic polymers can form complexes with mRNA vaccines through charge interactions. After cellular uptake, they enter acidic endosomes, where the positively charged polymers interact with negatively charged phospholipids on the endosomal membrane, disrupting it, inducing membrane fusion, and releasing the mRNA.	• Good stability	• Toxicity • Poor biocompatibility
Peptide Carrier	• Positively charged peptides used for nucleic acid delivery contain lysine and arginine residues, allowing them to form nanocomplexes with negatively charged mRNA via elec- trostatic interactions. These complexes are efficiently taken up by cells and enter endosomes. The peptides then interact with negatively charged phospholipids on the endosomal membrane, disrupting it, inducing fusion, and releasing mRNA.	• Relatively stable • Low immunogenicity • Low toxicity	• Some cationic peptides bind too tightly to mRNA, affecting its release.
Virus-like Replication Particle	• Virus-like replicon particles (VRPs) can encapsulate antigen- encoding mRNA and deliver it to the cytosol, mimicking viral infection.	• Ability to maintain self-replication	• Highly immunogenic • Somewhat toxic.

Delivery Strategy for mRNA Vacines

•EfectivedeliverymethodsremainamajorchalengeformRNAvacines.Curentdeliveryaproachesincludecarier-

basedelivery,nakedmRNAinjection,andendriticel(DC)delivery,withnakedmRNAinjectionandDCdelivery

primarilyusedintumormRNAvacinedevelopment.

•Amongcarierdeliverysystems,lipidnanoparticles(LNPs)arethemostwidelyusedtolforinvivomRNAdelivery.

Source: Literature Review, Frost & Sulivan

Overview of Subunit Vacines

•Subunitvacines,createdusingsyntheticpeptidesorecombinantechnology,areregardedasasafeandependable

aproach.NotablesubunitvacinesaprovedbytheFDAincludethoseforhumanpapilomavirus(HPV),hepatitisB,

andinfluenza.

•Asubunitvacinestrategy,whereonlyesentialmicrobialcomponentsnecesarytotrigerasuitableimuneresponse

(suchasprotein/peptideandcarbohydrateantigens)areadministered

•They can greatly enhance vacine safety.

•This aproach may also facilitate the development

of vacines in cases where traditional methods

have ben unsucesful, such as HIV vacines.

•Subunit vacines can be manufactured in a wel-

characterized form, improving batch consistency,

•They are designed to direct imune responses

toward specific microbial targets (epitopes).

•Aditionaly, they alow the integration of non-

natural components and can be freze-dried,

enabling transport and storage without

refrigeration.

Benefit:Type of Subunit vacine

Basic Design Proces:

1.Imunogenic subunit identification

2.Expresion and synthesis of subunit

3.Extraction and purification

4.Adjuvant adition or vector incorporation

5.Formulation and delivery

Recombinant Protein Vacines

Toxoid Vacines

Conjugate Vacines

Virus Like Particles

OMV Vacines

Recombinant vacines are produced by inserting viral or bacterial DNA into bacterial or

yeast cels, which then manufacture specific proteins from the pathogen. These proteins

are purified and used as the vacine’s active ingredient, like in hepatitis B vacine.

Toxoid vacines use inactivated bacterial toxins, resembling toxins but non-poisonous.

They stimulate the imune system to recognize and respond to toxins, providing

protection against bacteria that release harmful proteins.

Conjugate vacines enhance imune response by ataching polysacharides from

bacterial surfaces to a protein, usualy diphtheria or tetanus toxoid, which helps train the

imune system, especialy in infants and young children.

Virus-like particles (VLPs) mimic viruses without being infectious, lacking genetic

material. They self-asemble from viral proteins and efectively stimulate imune

responses by presenting multiple antigens, sometimes acting as adjuvants to enhance

imunity.

Outer Membrane Vesicles (OMVs) are non-infectious particles derived from bacterial

outer membranes, containing membrane antigens. In vacines, OMVs can be modified

to remove toxins, retain imunogenic antigens, and naturaly act as adjuvants.

Overview of Polysacharide Conjugate Vacines

•Chemicalconjugationwithacarierproteinsignificantlyenhancestheimunogenicityofweaklyimunogenicantigens

andisefectivelyusedinpolysacharideconjugatevacinedevelopmentagainstinfectiousdiseases.

•Thisaproachcovalentlybindspolysacharideandprotein,enhancingthepolysacharide’simunogenicpropertiesby

incorporatingtheprotein’sbeneficialcharacteristics.ItalsoprovidesanepitopeforCD4+Tcels,suportingamemory

responsetopolysacharidesandimprovingoveralimuneresponsedurability

Manufacture proces

To prepare a polysacharide conjugate

vacine, the polysacharide and carier protein

are purified, coupled chemicaly, then purified

again, quality-checked, and tested for

imunogenicity, resulting in the final vacine

product.

Mechanism of Action

The polysacharide conjugate vacine is procesed by antigen-presenting

cels, presenting glycan-peptides on MHC I, trigering IL-4 and IL-2 release,

which matures B cels into memory cels producing IgG antibodies.

Benefit

•More efective and long-lasting.

•The conjugate vacine provide long-term imunity andlong-lived T-

cel memory, which helps in recognizing and responding to future

infections.

•The conjugate vacine can generate a strong boster response upon

re-exposure to the antigen.

Production Complexity of Polysacharide Conjugate Vacines

•Thecomplexityofpolysacharide-conjugatedvacineproductionarisesfromchalengesrelatedtoantigenselection,

carierproteininterference,preciseantigenratios,serotypecompatibility,andqualitycontrolduringmanufacturing.

Overcomingthesechalengesrequirescarefulprocesdesignandoptimization,suchastheuseofQuality-by-Design

(QbD)methods,toensuretheficient,safe,andstableproductionofthevacine.

1. Antigen Selection and Serotype Integration

•A major chalenge is incorporating aditional serotypes into the vacine

without compromising safety, eficacy, and manufacturability. Key

considerations include:

•Antigen Selection: The right serotypes must be chosen based

on global prevalence and disease burden.

•Optimal Conjugation Chemistry: Ensuring eficient

conjugation of the polysacharides while maintaining their

stability.

•Carier Protein Selection: The choice of carier protein must

be carefuly considered to avoid interfering with the imune

response to the polysacharide antigens, especialy when

multiple serotype-specific polysacharides are conjugated to

the same carier protein.

2. Carier Protein Interference with Imune Response

•Carier proteins can interfere with the imune system’s response to

polysacharide antigens. This is especialy problematic when multiple

polysacharides from diferent serotypes are conjugated to the same

carier protein, potentialy leading to reduced vacine eficacy and

diminished serotype-specific imunity

3. Chalenges with Multivalent Vacines

•Compared to traditional monovalent vacines, higher-valent PCVs

(those with multiple serotypes) face aditional complexities, such as:

•Precise Antigen Ratios: High-valent vacines require precise

antigen ratios to ensure the corect imune response.

•Serotype Compatibility Isues: Compatibility betwen

diferent serotypes may cause chalenges in scaling up

production and optimizing yields, which in turn afects cost-

efectivenes and global availability.

4. Quality Control and Proces Optimization

•To adres the proces-related chalenges, the Quality-by-Design (QbD)

aproach must be implemented to ensure that quality is built into the

proces design. This aproach, as sugested by ICH-Q8 guidelines,

includes:

•Identifying Critical Quality Atributes (CQA), Critical Materials

Atributes (CMA), and Critical Proces Parameters (CP).

•Developing a control strategy and optimizing the production

proces through Design of Experiments (DoE), folowed by data

analysis to refine the proces.

Overview of recombinant vacines

•Recombinantvacinesareusualyproducedbybenefitingfrombacteria,yeast,mamalian,andinsectcels.Itinvolves

therecombinantexpresionofproteinsandviralvectors.Thistechnologyprovidestheposibilityofdevelopingvacines

againstdificult-to-cultureornon-culturablevirusesandeliminatesafetyrisksbyusingbioprocesesthataremore

controledwithdefinedprocescomponentsandashorterprocesofproduction,whichisveryimportantintermsof

respondingtoapandemic

Subtypes of Recombinant VacineBenefits of recombinant vacines:

•Recombinant vacines are safe, efective,

and the upstream proces in recombinant

vacine technology is fast compared to cel

culture and in eg production and does not

require the handling of live virus and the

acompanying expensive Biosafety

containment equipment.

•It is likely that more recombinant vacines

wil be developed in the future, providing

protection against even more diseases. In

adition, advances in genetic enginering

techniques and the use of novel vectors,

such as viral vectors and nanoparticles,

may further enhance the efectivenes of

recombinant vacines and expand their

potential aplications. These

developments could lead to the

development of vacines for diseases that

have ben dificult to target with traditional

vacine aproaches, such as cancer and

autoimune diseases.

RecombinantProtein Vacines

LiveRecombinant Vacinesusing bacterial or viral vectors

DNA Vacines

•Most of the recombinant vacines developed in the recent decays are clasified as

recombinant protein vacines. including hepatitis B and, more recently, HPV

•This aproach uses the capacity of infection and the imunological properties of the

live vector to elicit an imune response against its own proteins, as wel as towards

the heterologous protein being presented. A number of bacteria (such as Salmonela

typhi and bacile Calmete-Guérin (BCG) ) and viruses (such as vacinia and

adenovirus) have ben investigated as live recombinant vector vacines.

•Efectively stimulate the imune system as in natural infections and have intrinsic

adjuvant properties.

•DNA vacines involve the administration of a naked DNA plasmid directly into the

muscle, which has the capability to provoke an imune response and provide

protection against pathogens after chalenge.

•There is no risk of infection, contrary to atenuated vacines; they elicit both humoral

and cel-mediated imunity, and they are capable of inducing long-lived imune

responses and increased cytotoxic T-cel responses.

1	Overview of the human vaccine market

1.1	Overview of the vaccine industry background

1.2	Classification of vaccines by technical route

1.3	Overview of the Global Vaccine Market

1.4	Overview of the China Vaccine Market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

Boom of New Vaccines

Source: Frost & Sulivan

2000-20102000: Meningococal (group C)vacine

2000: Pneumococal (heptavalent pneumococal conjugate)vacine

2005: Meningococal (quadrivakentmeningococal conjugate)vacine

2006: Combined Hib vacine

2008: HPV

2010: PCV13 (13-valent pneumococal conjugate)

2010: First therapeutic vacine –Provengefor prostate cancer

2013Shingles: Children’s Influenza Rotavirus

Global Development History of the Vacine

•Thepastdecadeshavesentheaplicationofmoleculargeneticsanditsincreasedinsightsintoimunology,microbiologyand

genomicsapliedtovacines.CurentprogrescomprisesthedevelopmentofrecombinantmeningococalBvacineandnew

techniquesforseasonalinfluenzavacinesmanufacturing.Moleculargeneticsetsthesceneforabrightfutureforvacines,

includingthedevelopmentofnewvacinedeliverysystems(e.g.DNAvacines)andnewadjuvants,includingthedevelopmentof

efectivetuberculosisvacines,ebolavacines,HIV,etc.

1800s1885: Firstlive-atenuatedvacine–live-atenuated rabies

1886: Firstinactivatedvacine–cholera, plague, typhoid

1700s1798: Development of first smalpox vacine

1900s

2015Meningococal B: Meningococal ACWY

2017Hexavalent: DTaP/IPV/Hib/HepB

•The first smalpox vacine was developedin 1798. It

opened the dor for the development of vacines. In 18

century, Louis Pasteur’s experiments spearheaded the

development of live atenuatedcholera vacine and

inactivated anthrax vacines.

•From1890 to1950, bacterial vacine development

proliferated, including the Bacilis-Calmete-Guerin (BCG)

vacination, which is stil in use today.

•In 1972, recombinant DNA technology was established at

Stanford University, and subsequently aplied to vacine

development. Among genetic enginering vacines, the

recombinant hepatitis B vacine is more sucesful, which

has a beter imune efect.

•In the late 1980s and early 1990s, nucleic acids expresing

gene products were used for gene therapy experiments,

and they could induce an imune response in the body,

which set of a research bom in nucleic acid vacines.

•In 2020, the world’s first mRNA vacine has begun its

rolout after being produced at unprecedented sped as

part of the global efort to end the Covid-19 pandemic. The

two mRNA Covid-19 vacines –one made by

Pfizer/BioNTechand the other by Moderna–mark the first

time mRNA vacine technology has ben aproved for use.

Key takeaways

Source: Frost & Sulivan

2020First mRNA vacine -COVID-19 vacines, e.g. Pfizer, Moderna

1900s: Toxoid vacines –diphtheria and tetanus toxoids

1927: BCG

1936: Influenza vacine

1948: First combination vacines –diphtheria, tetanus and pertusis

1955: Subunit vacines –Polio (injected, inactivated) vacine

1970s: First polysacharide vacine

-Meningococal (meningococal polysacharides) vacine

-Pneumococal ( pneumococal polysacharides) vacine

1981: First recombinant antigen vacine -HBV

1999: Meningococal (group C) vacine

Year		Number of Vaccines Approved				Trade Name	Indications	Company Name
2019			3			DENGVAXIA	Dengue fever	Sanofi
						JYNNEOS	Smallpox, monkeypox	Bavarian Nordic
						ERVEBO	Ebola	MSD
2020				2		AUDENZ	Influenza	Seqirus
						MenQuadfi	Meningococcal disease	Sanofi
2021						PREHEVBRIO*	Hepatitis B	VBI Vaccines
3
						VAXNEUVANCE	Pneumococcal	MSD
						TICOVAC	Tick-borne encephalitis	Pfizer
2	022				2	IPOL	Poliomyelitis	Sanofi
2						PRIORIX	MMR	GSK
2023		5				CYFENDUS	Anthrax	Emergent BioSolutions
						Abrysyo	RSV	Pfizer
						Arexvy	RSV	GSK
						Penbraya	Meningococcal disease	Pfizer
						Ixchiq	Chikungunya virus	Valneva
2024			2			MRESVIA	RSV	Moderna
						CAPVAXIVE	Pneumococcal 21-valent Conjugate virus	Merck

5

Vacines Aproved by FDA in 2019-2024

Source: FDA, Frost & Sulivan

*Note: has ben voluntarily withdrawn from the market by the company

COVID-19 vacines are not included in the chart

Period CAGR 2019-2024 12.4% 2024-2033E 14.8% Unit: Billion RMB 331.9 295.0 258.8 222.9 188.4 156.0 132.1 120.5 113.9 92.6 94.1 96.1 100.9 74.4 53.5
2019 2020 2021 2022 2023 2024 2025E 2026E 2027E 2028E 2029E 2030E 2031E 2032E 2033E Note: The COVID-19 vaccine market has not been considered.

•Fromtheperspectiveofthevacineindustryasawhole,thereisnotmuchdiferenceinmarketsizebetwenthe

productionvalueandsalesdimensions

•COVID-19vacines,grewfromRMB53.5bilionin2019toRMB96.1bilionin2024,ataCAGRof12.4%.Drivenbythe

expectedcontinuouslaunchofinovativevacines,thevacinemarketinChinaisexpectedtofurthergrowto

RMB331.9bilionin2033,ataCAGRof14.8%from2024to2033.

China Human Vacine Market Size, 2019-2033E

Source: Anual Repot, Frost & Sulivan

China Human Vacine Market Size by Production Value, 2019-2033E

Period CAGR 2019-2024 6.0% 99.4 2024-2033E 8.0% 92.5 Unit: Billion USD 85.9 79.3 73.0 67.0 61.8 57.7 53.7 51.7 49.8 46.4 43.3 38.9 37.2
2019 2020 2021 2022 2023 2024 2025E 2026E 2027E 2028E 2029E 2030E 2031E 2032E 2033E Note: The COVID-19 vaccine market has not been considered.

Global Human Vacine Market Size, 2019-2033E

•Theglobalvacinemarket,intermsofsalesrevenueandwithoutconsideringCOVID-19vacines,increasedfrom

US$37.2bilionin2019toUS$49.8bilionin2024,ataCAGRof6.0%.Drivenbythecontinuouscomercializationof

inovativevacinesandmarketgrowthinemergingcountries,suchasChina,theglobalvacinemarketisexpectedto

reachUS$99.4bilionin2033ataCAGRof8.0%from2024to2033.

Global Human Vacine Market Size, 2019-2033E

Source: Anual Repot, Frost & Sulivan

Global Vacination Situation, Chalenges and Neds

•InApril2021,theWorldHealthOrganization(WHO),theUnitedNationsChildren’sFund(UNICEF)andtheGlobalAliancefor

VacinesandImunization(GAVI),amongotherorganizations,anouncedtheImunizationAgenda2030,whichseksto

promotevacinationtoprotectpeopleofalagesfromdisease.Athesametime,theAgendaforImunizationcalsonthe

pharmaceuticalindustryandresearcherstostrengthencolaborationwithgovernmentsandfunderstoaceleratevacineresearch

andevelopmentandensureasustainedsuplyofafordablevacines.

Low Vacine

Acesibility

Wide Variation in

Vacination Rates

Major Developments and Chalenges

•Developing countries

have limited medical

resources compared

to developed regions.

•Developing countries

have low vacine

acesibility due to

insuficient capacity of

vacine resources,

dependence on a few

manufacturers, and

safety lapses in the

production proces.

High Price of

Vacines

•Countries not covered

by GAVI pay high

prices for vacines.

•Unafordable vacine

prices not only limit a

country’s ability to

expand vacine

coverage, but also

discourage the

introduction of new

vacines, which can

further reduce

vacination rates.

•The reasons for the

wide variation in

vacination rates

among GAVI are

highly corelated with

national economies.

•In Ethiopia, where

les than 40% of

children have

received basic

vacinations,

vacination rates are

relatively low.

Neds of Developing

Countries

•Increase vacine coverage: direct

more GAVI funds to regions with

low coverage (e.g., Asia, Africa,

Latin America).

•Save on vacine costs: control

prices through centralized

purchasing and pricing

agrements.

•Improve acesibility: developing

countries adopt colaborative

vacination models to sped

introductions, ensure quality, and

expand the Vacine Asistance

Program (VAP) for stronger

national imunization programs.

Source: Literature Review, Frost & Sulivan

1	Overview of the human vaccine market

1.1	Overview of the vaccine industry background

1.2	Classification of vaccines by technical route

1.3	Overview of the Global Vaccine Market

1.4	Overview of the China Vaccine Market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

Year	Number of Vaccines Approved	Trade Name	Indications	Company Name
2019	4 1 5	Quadrivalent influenza virus split vaccine	Influenza	GDK （金迪克生物）
		SHINGRIX	Herpes zoster	GSK
		Varicella vaccine	Varicella	SINOVAC （科兴生物）
		WEUPHORIA （沃安欣）	Pneumonia	WALVAX （沃森生物）
		Cecolin （馨可宁）	Cervical carcinoma	WantaiBioPharm （万泰生物）
2020	5 5	Wugan （雾感）	Influenza	BCHT （百克生物）
		Diphtheria,Tetanusand Acellular Pertussis Combined Vaccine， Adsorbed	Diphtheria, Tetanus and Acellular Pertussis	Minhai （民海生物）
		Group A and Group C Meningococcal Conjugate Vaccine	Cerebrospinal meningitis	OLYMVAX （欧林生物）
		Influenza Vaccine (Split Virion), Inactivated, Quadrivalent	Influenza	SINOVAC （科兴生物）
		23-valent Pneumococcal Polysaccharide Vaccine	Pneumonia	SINOVAC （科兴生物）

4 1 5

4	1

5 5

Vacines Aproved by NMPA in 2019-2024

Source: NMPA, Frost & Sulivan analysis

Domestic Vacines

Import Vacines

Year	Number of Vaccines Approved	Trade Name	Indications	Company Name
2021		Menphecia （美奈喜）	Cerebrospinal meningitis, pneumonia	CanSinoBIO （康希诺生物）
		Menhycia （曼海欣）	Cerebrospinal meningitis, pneumonia	CanSinoBIO （康希诺生物）
		Rabies Vaccine (Vero Cell), Freeze- dried	Rabies	YIDU Biotechnology （亦度生物）
		Weiminfeibao （维民菲宝）	Pneumonia	Minhai （民海生物）
8 8
		HaemophilusInfluenza Type b Conjugate Vaccine	Cerebrospinal meningitis, pneumonia	Minhai （民海生物）
		Poliomyelitis Vaccine (Vero Cell)， Inactivated, Sabin Strains	Poliomyelitis	SINOVAC （科兴生物）
		Influenza Vaccine (Split Virion), Inactivated, Quadrivalent	Influenza	Shanghai institute of biological products （上海生物制品研究所）
		Rabies Vaccine (Vero Cell), Freeze- dried	Rabies	Changchun institute of biological products （长春生物制品研究所）
2022	2 1 3	AdimFlu-S （安定伏）	Influenza	ADIMMUNE （国光生物）
		Walrinvax （沃泽惠）	HPV	WALVAX （沃森生物）
		Group ACYW135 Meningococcal polysaccharide vaccine	Cerebrospinal meningitis	Beijing institute of biological products （北京生物制品研究所）

2 1 3

2	1

Vacines Aproved by NMPA in 2019-2024

Source: NMPA, Frost & Sulivan analysis

Domestic Vacines

Import Vacines

Year	Number of Vaccines Approved	Trade Name	Indications	Company Name
2023	8 1 9	live attenuated zoster vaccine （感维）	Herpes Zoster	BCHT （百克生物）
		freeze-dried rabies vaccine, verocell	Rabies	Hualan Biological Bacterin （华兰生物）
		Tetanus Vaccine, Adsorbed	Tetanus	Hualan Biological Bacterin （华兰生物）
		VaxigripTetra （凡尔佳）	Influenza	Sanofi
		ROTALAN （瑞特威）	Rotavirus gastroenteritis	Lanzhou institute of biological products （兰州生物制品研究所）
		Quadrivalent Subunit Influenza Vaccine （慧尔康欣）	Influenza	Ab&bBio-Tech （中慧元通）
		23-Valent Pneumococcal Polysaccharide Vaccine	Pneumonia	ZFSW （智飞生物）
		freeze-dried rabies vaccine	Rabies	MINHAI （民海生物）
		freeze-dried rabies vaccine, verocell	Rabies	CuroVax （康润生物）
2024	2 2	Freeze-dried Rabies Vaccine (Vero Cell) for Human use	Rabies	Aleph （复星雅立峰）
2024	2 2	Varicella Vaccine, Live	Varicella	MINHAI （民海生物）

8	1

Vacines Aproved by NMPA in 2019-2024

Source: NMPA, Frost & Sulivan analysis

Domestic Vacines

Import Vacines

	2 – 3 years	3 – 6 years

Introduction to the ful lifecycle proces of Chinese vacines and

average years of research and development

Source: Frost & Sulivan

Research (including imunology)

Pre-clinical development

Clinical development (including post-marketing surveilance)

Transfer proces to manufacturing

1 years

•The development of a new vacine can be divided into research, pre-clinical testing, clinical testing, and post-marketing

surveilance. It usualy takes more than 15 years from identifying the antigens to come to the market.

•Duringtheclinicaltrialsofvacines,thepurposeofphaseIisto testhesafetyofthevacinesonhealthyadults.After

thephaseIiscompleted,phaseIisconductedtoevaluatewhetherthevacinescanmethexpectedefects

(imunogenicity)andobtainthesafetyinformation.ThegoalofphaseIistoevaluatetheficacyandsafetyofthe

vacine,whichisaesentialphaseforobtainingaprovalforegistration.

Identify

antigens

Produce

antigens

Pre-

clinical

Phase IPhase IPhase ILaunch

Post-

marketing

surveilance

>90%	92%	57%	30-40%	95%	58%	35%
9%	44%	<1%		93%	71%	<1%

80%

Comparison of Vacination Coverage in China, United States and

GAVI Countries

Source: Frost & Sulivan

•The vacination rate of comon vacines available in the market is exhibited as below. For Category I like DTaP, the vacinationrate

in China almost verges on the level in U.S. meanwhile GAVI countries also exhibits considerable vacination rate with aids ofcharitable

funds over the recent years. Rather, the vacination rate of Category I in China is highly limited by now when compared withthe

vacination level in the U.S. as indicated below. Above 90% of people in the U.S. has ben vacinated with pneumococal vacines

while merely 9% of people in China received such vacine. Furthermore, les than 1% of people in China has ben vacinated with

HPV. Such diference unveils a great market potential in vacine industry in China, especialy for Category I vacines.

Country

Pneumococ

cal Vacines

Hib

Vacines

HPV

Influenza

Vacines

•Due to diferent imunization programs in China and U.S., the vacination rate of Category I and Category I vacines is not aplicable above.

•The vacination coverage of pneumococal vacines shown above refer to the sum coverage of PCV7 and PCV13 vacination among children in the U.S.

and PSV23 coverage among children and elderly (>65 years) in China, respectively.

•The HPV coverage shown is the vacination coverage in female at the age of 13-17 years in the U.S. and that in female at the ageof 9-15 years in China.

DTaP

81%

% of Children Imunized in 73 GAVI Countries (Mostly

Consists of Category I Vacine)

Note:

Covid 19Shingles

Regulations in Vacine Value Chain in China

Source: Government Anouncement, Frost & Sulivan analysis

•China has imposed stricter rules over the entire value chain of the vacine industry. Tighter regulation from R&D to

inoculation promises higher quality of vacines and help stamp out ilegal behaviors in the vacine industry. China’s

state council has oficialy amended rules for vacine circulation and vacination by baning wholesalers from direct

sales to clinics at the provincial and country levers where purchase is centralized. Great eforts has ben invested to

strengthen the cold chain storage, transportation, traceability management system throughout the vacine distribution

proces. Revised regulatory requirements such as beter record keping for the production, storing and transport of

vacines and tougher punishment for the lawbreakers is beneficial for public heath.

Manufacturing

R&D

Registration

Distribution

Sales

Vacination

Regulators

CFDA, MOEP

CFDA

SAMR, CFDA

NIFDC

CFDA

SCPC

Documents

GMP, Emision standard of water

polutants for pharmaceutical industry

《制药工业水污染物排放标准》

Technical Guidelines for Preclinical

Research on Preventive Vacines

《预防用疫苗临床前研究技术指导》(2010)

Provisions for Drug Registration (2020)

《药品注册管理办法》(2020)

Administrative Measures for Batch

Release of Biological Products (2020)

《生物制品批签发管理办法》(2020)

GSP, Measures for the supervision and

administration of circulation of

pharmaceuticals

《药品流通监督管理办法》(2016)

Vacine Administration Law of the

People’s Republic of China

《中华人民共和国疫苗管理法》(2016)

Main Content

•To determine the focus of supervision and clear person responsible.

•To optimize the risk management proces, material reviewing, and

specifying the timeframe for the lot release and reinforce

administration.

•Implementation of the Marketing Authorization Holder (MAH) system.

•To establish a prioritized review and aproval system, and

implementation of data protection towards data submited by

aplicants for inovative drugs, orphan drugs, and child-specific drugs.

•To acelerate the proces of drug reviews and aproval, the State

Drug Administration is required to conduct a formal review of the

aplication materials within 5 working days.

•To determine the focus of supervision and clear person responsible.

•Vacine products should be completed within 60 days of Lot Release.

•To reform the distribution of clas I vacine and eliminate the multiple

intermediate wholesalers in the vacine industry.

•To increase penalties and acountability to further punish the ilegal

conduct and inefective supervision during vacine distribution.

•Supervise the whole proces of vacine development, production,

distribution and vacination. Ensure the quality and suply of vacines

and standardize vacination

Entry Bariers of Human Vacines Market in China(1/2)

Market Aces

Bariers

•High industry entry bariers: In terms of vacine production management, the state

implements a strict aces system for vacine production and strictly controls the

establishment of new vacine production enterprises. There is strict supervision in al aspects

of vacine production, circulation and supervision in China.

•High capital neds: Companies ned to invest heavily in developing new vacines. The

construction of R&D facilities, manufacturing facilities, testing, and clinical trials al require

significant capital expenditures.

•High production costs: The vacine industry has low capacity utilization, and a production line

can usualy only produce one vacine, resulting in high production fixed costs.

•Fierce competition: The competition presure of vacine varieties is high, and the profit

margin of enterprises is compresed. Developing core technologies independently is the key

to sustainable and healthy development.

Sales Chanel

Bariers

•Strict management of vacine circulation: vacine manufacturers ned to entrust enterprises

with cold chain storage and transportation conditions for distribution or entrust themselves with

cold chain storage and transportation conditions.

•From the vacine manufactures to end users, the vacine distribution chanel involves multiple

parties. CDCs and the government plays a very important role in the vacine biding, purchase

and distribution proces. The vacine manufacturers should build a solid relationship with

diferent parties and expand their sales chanels. Through the long-term eforts of developing

and maintaining distribution chanels, vacine manufacturers distribute safe and qualitative

vacines to end users.

•Industry leaders have a high market share with high brand maturity, causing fierce competition.

Source: Frost & Sulivan Analysis

Entry Bariers Human Vacines Market in China(2/2)

Technology and

Talent Bariers

•Thevacinedevelopmentprocesisverycomplex.KeyR&Dcapabilitiesincludeplatform

technologyandadvanced,adequateR&Dfacilitiesandequipment.

•Newentrantslackexperiencedtalentwithspecializedknowledge.

•Thevacinedevelopmentprocesiscomplexwithalongtimeline,requiringexperienced

technicians.China’svacineindustrylackofseniorandmidlemanagementpersonel.Athe

sametime,thetrainingofpersonelrequirestimeandexpenditure.

•Duetothedificultyofnewvacineresearchandevelopment,somenterpriseshave

licensed-inthetechnologyfromacompanywithmatureproductiontechnology.However,the

productiontechnologyandindustrializationofnewvacinesarestildificult,especialyfor

enterpriseslackingcorespondingtechnicalcapabilities,forminghighvacinetechnicalbariers.

Production

Quality

Management

Bariers

•China implements a strict aces system for vacine production and strictly controls the

establishment of new vacine manufacturers. In adition to meting the requirements for the

establishment of vacine manufacturers, newly established vacine manufacturers shal also

comply with the relevant policies of the national vacine industry authorities.

•Biological products, including vacines, are distinguished from chemical pharmaceuticals by

being derived from living organisms with a molecular composition to complex to be defined by

physical or chemical means. In adition, the inherent variability of living organisms, and the

potential for contamination of materials with agents coming from starting materials or the

environment, require special quality control and quality asurance mechanisms.

Regulatory

Bariers

•Thevacineindustryisahighlyadministrativelysupervisedindustry,whichistrictlysupervised

andcontroledbythecompetentgovernmentauthoritiesfromresearchandevelopment,

production,circulation,salesandafter-salesafety

Source: Frost & Sulivan Analysis

Date	Government	Policies	Comments
Feb 2006	State Council	Notice of the State Council on Issuing the “the National Outlines for Medium and Long-term Planning for Scientific and Technological Development(2006-2020)” (《国务院关于印发《国家中长期科学和技术发展规划纲要(2006- 2020年)》的通知）》)	Create an incentive environment for independent innovations. The endeavor will construct a innovation-oriented state, establish an accreditation system for national independent innovation products and regulate the accreditation of independent innovation products.
Dec 2007	Ministry of Health	Notice of the Ministry of Health on Issuing the “Expanded National Immunization Program Implementation Plans” (《卫生部关于印发《扩大国家免疫规划实施方案》的通知》)	The national immunization plan will be upgraded from 6 vaccines that can prevent 7 types of diseases to 14 vaccines that can prevent 15 types of diseases, including hepatitis A and meningitis.
June 2009	State Council	Notice of the State Council on Issuing the “Several Policies to Promote the Accelerated Development of the Biological Industry”(《促进生物产业加快发展的若干政策》)	Promote the industrialization of biotechnology R&D and innovation, build major biotechnology infrastructures, and make further breakthroughs in key technologies such as therapeutic vaccines and antibodies, cell therapy, genetically modified crop breeding, and bioenergy crop cultivation. Innovative products such as influenza vaccine, molecular diagnostic reagents, super rice, and polylactic acid should be promote and applied.
Oct 2010	State Council	Decision of the State Council on Accelerating the Fostering and Development of Strategic Emerging Industries (《国务院关于加快培育和发展战略性新兴产业的决定》)	Promote biotechnological medicine, novel vaccine and diagnostic agents, chemical drugs, modern traditional Chinese medicine, and related types of innovative drugs in the treatment and prevention of major diseases. Elevate the level of the Chinese biopharmaceutical industry.
Dec 2011	State Council	The State Council on forwarding the Development and Reform Commission and other departments Notice of the Vaccine Supply System Construction Plan（《国务院办公厅关于转发发展改革委等部门疫苗供应体系建设规划的通知》）	Construct the vaccine supply system to fit the demand of the Chinese societal and economic advancement by 2015. By 2020, the goal is to further complete the system to prepare for major emergency response through promoting legal infrastructure and standard systems, furthering financial supportive policies, expanding the R&D budget, investing in human resources, and strengthening the coordination among the vaccine supply system.

Regulations of Vacine Market in China -I

Source: Government Anouncement, Frost & Sulivan analysis

Date	Government	Policies	Comments
Dec 2012	State Council	Notice of the State Council on Issuing the Bio- Industry Development Plan（《国务院关于印发生物产业发展规划的通知》）	Improve the pharmaceutical management system and mechanisms, comprehensively enhance the innovation capabilities and product quality management capabilities of biomedical companies. Also accelerate the development and industrialization of new products and new processes such as biotechnology drugs, chemical drugs, and traditional Chinese medicines, enhance regional supporting capabilities, and actively promote the industry structural adjustments will make the biomedical industry bigger and stronger. The policy also emphasize the development and industrialization of novel vaccine, including the ones for therapeutic purposes.
May 2015	State Council	Notice of the State Council on Issuing the “Made in China (2025)” (《国务院关于印发《中国制造 2025》的通知》)	Encourage R&D of new biotech drugs for major diseases, focusing on novel vaccines.
April 2016	State Council	Decision of the State Council on Amending the Regulation on the Administration of Circulation and Vaccination of Vaccines(《国务院关于修改《疫苗流通和预防接种管理条例》的决定》)	Vaccine production enterprises shall distribute Category-II vaccines directly to county disease prevention or authorize enterprises with cold chain storage transport conditions.Vaccines should be stored and transported in the environment with the prescribed temperature during entire distribution process. Information of vaccine manufacturing, storage, transport and uses should has track record.
Dec 2016	State Council	Notice of the State Council on Issuing the “National strategic emerging industry plan during 13th Five- Year Plan Period” (《国务院关于印发“十三五”国家战略性新兴产业发展规划的通知》)	The policy aims to build a new system in in biopharmaceutical industry. It pushes for the development of novel drugs and innovative biopharmaceutical products. Also promote and spread green, smart drug manufacturing technology. Strengthen efficient management and policy support for more industry globalization.
Dec 2016	Development and Reform Commission	Notice of Development and Reform Commission on issuing “The biological industry development plan during 13th Five-Year Plan Period” 《发展改革委印发“十三五” 生物产业发展规划的通知》)	The goal to promote the scale of the Chinese biopharmaceutical industry and to help advance the industry to become the leader of the national economy. The policy also encourages the development of therapeutic vaccine, innovating safe and effective Live vector genetic engineering multivalent vaccine.

Regulations of Vacine Market in China -I

Source: Government Anouncement, Frost & Sulivan analysis

Date	Government	Policies	Comments
Jan 2017	State Council	Notice of the State Council on Issuing the Plan for Medicine and Health during 13th Five-Year Plan Period (《国务院关于印发“十三五”卫生与健康规划的通知》)	Improve centralized purchasing of vaccine for hospitals, cold chain management.Standardize regulations to manage vaccination of vaccinesin clinics. Aim to establish vaccination abnormal response compensation insurance mechanism. Sales of unapproved vaccine are strictly forbidden.
Feb 2017	State Council	Opinion of the State Council on further enhancing Management of Vaccine and Immunization (《国务院办公厅关于进一步加强疫苗流通和预防接种管理工作的意见》)	All regions should enhance vaccine inspection capabilities. Establish professional drug inspectors team and promote standardized training. Gradually improve capabilities of provincial Foodand Drug Administration on vaccine testing.
Feb 2017	State Council	Notice of the State Council on Issuing the Plan for National Drug Safety during 13th Five-Year Plan “Period（《国务院关于印发 “十三五”国家药品安全规划的通知》）	Improve national vaccine approval system thereby enhance vaccine quality evaluation. In line with international standards, establish cell source database, stem cell database. Establish and improve the standard of biological products research and supply platform, quality evaluation criteria and technology platform.
Sep 2017	Beijing Health Committee	Measures of Beijing Municipality on the Administration of Vaccination Outpatients (2017) (《北京市预防接种门诊管理办法》 (2017版))	Setting up vaccination clinics must meet the following conditions at the same time:1. Have the medical institution practice license 2. Vaccination staff shall have the qualification of licensed physician, licensed assistant physician or nurse, regularly participate in the professional training of vaccination organized by the District Health and Family Planning Commission and pass the examination 3. It conforms to the setting standards of vaccination clinics in Beijing, and has passed the on-site acceptance and regular assessment organized by the District Health and Family Planning Commission. 4. Establish and earnestly implement various vaccination management systems to ensure the standardization and safety of vaccine and cold chain use and management, vaccination services.

Regulations of Vacine Market in China –I

Source: Government Anouncement, Frost & Sulivan analysis

Date	Government	Policies	Comments
Jun 2019	National People’s Congress	Vaccine Administration Law of the People’s Republic of China（《中华人民共和国疫苗管理法》）	Units and individuals engaged in vaccine development, production, distribution and vaccination activities shall abide by laws, regulations, rules, standards and norms, ensure the authenticity, accuracy, integrity and traceability of information throughout the process, assume responsibilities according to law and accept social supervision. Disease prevention and control institutions and vaccination units shall truthfully record the circulation of vaccines, vaccination and other information according to law, and provide traceability information to the national vaccine electronic traceability collaboration platform according to regulations. Disease prevention and control institutions, vaccination units, vaccine marketing license holders, and vaccine distribution units shall abide by the vaccine storage and transportation management specifications to ensure the vaccine quality. In addition to the vaccine fee, the vaccination unit may also charge the vaccination service fee for the vaccination of non immunization planned vaccines. The charging standards for vaccination service fees shall be formulated by the competent pricing departments of the people’s governments of provinces, autonomous regions and municipalities directly under the Central Government in conjunction with the financial departments.
Oct 2019	Development and Reform Commission	Decision of the National Development and Reform Commission on Amending the Relevant Entries under the Catalogue for Guiding Industrial Restructuring（Version 2019）（发展改革委修订发布《产业结构调整指导目录（2019年本）》）	Listing major disease prevention and treatment vaccines, antibody drugs, gene medicine therapy, cell medicine therapy, recombinant protein drugs, and other modern biotechnology reformed drugs as encouraged industries with supportive policies.
Jul 2022	State Food and Drug Administration	《Regulations on the Administration of Vaccine Production and Distribution》(No. 55 in 2022) （《疫苗生产流通管理规定》（2022年第55号））	Further refine the relevant regulations that enterprises and regulatory authorities need to comply with in all aspects of vaccine production, circulation and supervision. The holder is responsible for the whole process of vaccine. In terms of commissioned production, it is required to meet strict conditions before commissioned production, and all vaccine production processes must be commissioned. During the circulation of vaccine, the holder shall be responsible for the vaccine quality and must comply with the requirements of the whole process electronic traceability system.

Regulations of Vacine Market in China –Ⅳ

Source: Government Anouncement, Frost & Sulivan analysis

Approved Class II Vaccines
Classified by indications

Overview of Clas I Vacines in China

•Acording to the Regulations on the Administration of Vacine Circulation and Vacination, Chinese vacines can be

divided into imunization plan vacines and non imunization plan vacines based on the payment subject of

vacination fes. Imunization vacines and non imunization vacines are relative, not absolute constants. As

conditions mature, many non imunization program vacines wil also be included in the national imunization program.

Manufacturer

Population

Price

Introduction

The price of clas I vacines is relatively high

•Clas I vacines are paid by the recipient or

insurance company; With the improvement of

China’s disposable income level and health

awarenes, more and more residents have the

ability to chose clas I vacines as their health

investment to prevent certain diseases

Clas I Vacine

•Through the provincial centralized biding platform,

production enterprises are responsible for directly

conecting and delivering vacines to vacination

sites, and recipients ned to pay for them

themselves

Targeting a wider age group

Source: Frost & Sulivan

Hepatitis B vacine

Varicela vacine

2Tick-borne

encephalitis vacine

Rabies vacineInfluenza vacine

Enterovirus vacine

Brucela vacine

Pneumococal

vacine

4Yelow fever vacine

JE vacine

Cholera vacinePlague vacine

meningitis

Rotavirus vacineHepatitis E vacine

Typhoid vacineHPV vacine…

Note:

1. There are JE, meningitis and hepatitis B vacines in botnthe imunization planing vacines and non imunization planing vacines;

2. Freze dried varicela atenuated live vacine is managed as an imunization plan vacine in emergency vacination in Beijing, Tianjin and other areas;

3. Influenza virus split vacine is administered as an imunization program vacine for the elderly and students in Beijing;

4. The 23 valent pneumococal polysacharide vacine is administered as an imunization program vacine for elderly people aged 60 and above in Shanghai;

5. The above clasification has not ben included in the COVID-19 vacine. At present, the cost of COVID-19 vacine and vacination is shared by the medical insurance

fund and financial funds

•The steady economic growth in China has improved Chinese citizens‘ afordability and increased

healthcare spending on vacination as wel as provided more aceses to vacination services. The

healthcare expenditure per capita in China was about RMB2,460 in 2023, and there is a potential to

further increase in the future. Moreover, the Chinese disposable income per capita has grown rapidly,

increasing from RMB28,228.0 in 2018 to RMB39,218.0 in 2023, and this trend is expected to continue,

enhancing the wilingnes and ability to pay for vacines.

Increasing

Afordability and

Wilingnes to Pay

Growth Drivers of Clas I Vacine Market in China

Source: Frost & Sulivan analysis

•Chinese residents have paid more atention on the disease prevention and have more knowledge about

diferent types of vacination, such as HPV vacines. Increasing awarenes of both pediatric and adult

vacination, created by direct marketing eforts, promotional activities by the companies and increasing

education level, is driving the market growth. Curently, companies are promoting vacination through

marketing activities and providing vacine education through online education and consultation,

literature and documentaries. Al these activities have led to an increase of demand in China vacine

market.

Increasing

Awarenes of

Vacination

•Along with the improvement of technology in the vacine development, such as transfer from traditional

cel-culture technology to the aplication of bioreactor technology, the quality and eficacy of vacine are

significantly improved. With the upgrading technology, vacine manufactures can provide new types of

vacines to met customers’ demand.

Rapid Development

of Technology

Establish a Coordinative Mechanism for Vaccine Supervision	Achieve Whole Process ElectronicTraceability

Vaccine Marketing License Holders
Vaccine Electronic Traceability Systems

Medical Products Administration of The State Council & The Competent Health Department of The State Council National Vaccine Electronic Traceability Collaboration Platform		CDCs at All Levels VaccinationEntities
National Vaccine Electronic Traceability Collaboration Platform

Analysis of Regulations on Vacine Administration in China

Source: Government documents, Frost & Sulivan analysis

•The promulgation of the Vacine Administration Law of the People’s Republic of China aims to establish a

cordination mechanism and achieve ful electronic traceability. The preventive vacine industry has entered an era of

strong supervision.

National Health

Comision of

PRC

Other Relevant

Departments of

The State

Council

National

Medical

Products

Administration

Vacine

Administration

Law of PRC

The Drug

Regulatory

Department of

The People’s

Government of

The Province,

Autonomous

Region or

Municipality

The Apropriate Medical and Health

Departments of The Local Governments at

or above The County Level

Local Drug

Regulatory

Institution at

The County

Level

Other

Relevant

Departments

of The Local

Governments

at or above

The County

Level

Vacine

Supervision

Vacine

Management

Vacine

Safety

Vacine

Situation

Vacine

Suply

•The medical products administration of the State Council shal be responsible for

the supervision and administration of vacines nationwide. The competent health

department of the State Council shal be responsible for the supervision and

administration of vacination nationwide. Other relevant departments of the State

Council shal be responsible for supervision and administration relating to

vacines within the scope of their respective functions.

•The medical products administration of the State Councilshal, in

conjunction with the competent health department of the State Council,

formulate uniform vacine traceability standards and rules, establish a

national vacine electronic traceability colaboration platform, and

integrate whole proces traceability information on vacine production,

circulation and vacination so as to realize the traceability of vacines.

•Vacine marketing license holders shal establish vacine electronic

traceability systems, and link them with the national vacine electronic

traceability colaboration platform so as to realize traceable and

verifiable vacines of the minimum packaging unit in the whole proces

of production, circulation and vacination.

•Disease prevention and control institutions and inoculation

entities shal truthfuly record vacine circulation, vacination and

other circumstances in acordance with the law, and provide

traceability information to the national vacine electronic traceability

colaboration platform as required.

Vacine Traceability

Administration of Vacine Lot Release in China

•Lot release of biological products in these Provisions refers to the proces of reviewing and testing for vacine products,

blod products, in vitro diagnostic reagents for blod screning obtained marketing authorization and other biological

products specified by National Medical Products Administration (NMPA), prior to marketing or importation, and isuing

the lot release certification by designated lot release institutions.

•Products failing to pas lot release shal not be marketed or imported. Products exempted from lot release as aproved

by the NMPA in acordance with the law shal be excluded.

Provisions for the Lot Release of Biological Products

Aproval to

manufacturing

and seling

Centralized

purchasing at

provincial level

Lot release

aplication

Authority

Coverage

Standards

•NMPA：The NMPA shal be in charge of lot release of biological products

nationwide, specifies the scope of product varieties subject to lot release, designates

lot release institutions, clarifies the requirements for lot release and guides the

implementation of lot release.

•Drug regulatory departments of provinces, autonomous regions or

municipalities ：responsible for the supervision and administration of lot release

aplicants within their own administrative regions and for organizing on-site inspection

of products subject to lot release within their own administrative regions; shal asist

lot release institutions to cary out on-site inspection, organize on-site sampling of

products for lot release and disposal of non-conforming products in lot release

•Lot release of biological products in these Provisions refers to the

proces of reviewing and testing for vacine products, blod

products, in vitro diagnostic reagents for blod screning obtained

marketing authorization and other biological products specified by

NMPA, prior to marketing or importation, and isuing the lot release

certification by designated lot release institutions.

•Lot release products shal be manufactured in acordance with the

aproved proces and shal conform to the national drug standards

and drug registration standards.

Key points

•Since the implementation of lot release of

biological products in 2002, NMPA has

gradualy expanded the scope of the

vacine batch release system.

•By 2016, lot release management of al

marketed vacines were realized.

•In December 2020, NMPA isued a new

version of Provisions for the Lot Release

of Biological Products: For the lot release

of vacines, dosier review and sample

testing shal be conducted lot by lot; In

the proces of the lot release of specific

variety, the lot release institution may

make a comprehensive evaluation

acording to the proces and quality

control maturity of the variety and

previous lot release and dynamicaly

adjust the testing items and testing

frequency of the variety.

Source: Government Anouncement, Frost & Sulivan Analysis

Growth Drivers and Future Trends of China Vacine Market

Source: Frost & Sulivan Analysis

Technical

development and

availability of new

vacines

•China’s vacine industry has advanced significantly, covering both Clas I vacines and Clas I vacines. Continuous R&D

eforts focus on improving existing vacines and developing next-generation vacines for diseases such as rabies, malaria,

HPV and tuberculosis. Inovations like launch of EV71 vacine for HFMD, COVID-19 vacines and domestic PCV13 vacines,

highlight the strong R&D capabilities of domestic companies. These eforts are enhancing vacine atributes, including

aceptability, cost-efectivenes and protection. Companies with robust technical platforms are wel-positioned to optimize the

design of new vacines, aligning with market neds and expanding production to met regional demand. Advances in

biotechnology, such as the shift to bioreactor technology, have also improved vacine quality and eficacy. This technological

progres alows manufacturers to ofer new vacine products that beter met consumer demands. Such focus on technological

development and inovation is poised to drive significant growth in the Chinese vacine market.

Favorable policies

•TheChinesegovernmenthasintroducedseveralpoliciestostimulatethevacinemarket.InitiativesuchastheGuidelinesof

thePlanforDevelopmentofthePharmaceuticalIndustry(《医药工业发展规划指南》)andtheHealthandWelnesPlaninthe

ThirtenthFive-YearPlan(《“十三五”卫生与健康规划》)focusonpromotingR&Dformultivalentvacinesandexpanding

nationalimunizationprograms.Thesepoliciesunderlinethestrategicpriorityondiseaseprevention,therebydrivingmarket

expansion.Inadition,policiesuchasthe“OpinionsonFurtherStrengtheningVacineCirculationandVacination

Management”(《关于进一步加强疫苗流通和预防接种管理工作的意见》)promotelarge-scaleproductionofdomesticvacines

andindustrializationofnewvacines,particularlyforcombinationvacinesandmultivalentvacines.Asaresult,domestic

vacinemanufacturersarexpectedtogainsignificantmarketshareinthe

•ClasIvacinemarket.

Increasing

Afordability and

Awarenes of

Vacines

•EconomicgrowthinChinahasimprovedafordabilityandhealthcarespendingonvacines.Increasedhealthawarenes,

especialyafterCOVID-19,isbostingvacinationrates.Risingdisposableincomehasfurtherenhancedtheabilityand

wilingnesofcitizenstopayforvacines.

Resistance to

therapeutic drugs

and lack of efective

treatments

•Drugresistanceandtheabsenceofefectivetreatmentsforinfectiousdiseaseslikerabiesunderscoretheimportanceof

vacination.Thisrealizationhaspromptedgreaterpromotionandadoptionofvacines,thusfuelingmarketgrowth.

•China’salignmentwithinternationalstandards,evidencedbyWHOpre-certificationeligibilityandInternationalCouncilfor

HarmonizationofTechnicalRequirementsforPharmaceuticalsforHumanUse(ICH)membership,positionsdomestic

manufacturerstoexpandglobaly.Thiscomitmentometinglobalbenchmarksislikelytopenewinternationalmarkets.

Being geared to

international

standards

Growth Drivers and Future Trends of China Vacine Market

Source: Frost & Sulivan analysis

Developing

multivalent and

combination

vacines

•Thedemandformultivalentandcombinationvacinesisrising,drivenbytheirefectivenesinpreventingmultiplediseases.

Whileglobalcompaniescurentlydominate,severalChinesefirmsareworkingondevelopingnewmultivalentvacinestomet

growingdemand.

1	Overview of the human vaccine market

1.1	Overview of the vaccine industry background

1.2	Classification of vaccines by technical route

1.3	Overview of the Global Vaccine Market

1.4	Overview of the China Vaccine Market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

Types of Influenza Viruses

•Most experts believe that flu viruses

spread mainly by tiny droplets made

when people with flu cough, sneze

or talk. These droplets can land in the

mouths or nosesof people who are

nearby. Les often, a person might get

flu by touching a surface or object

that has flu virus on it and then

touching their own mouth, nose or

posibly their eyes.

Transmision

•There are four types of influenza viruses: A, B, C and D.

•Human influenza A and B viruses cause seasonal epidemics of disease (known as the flu season) almost every

winter in the United States.

•Influenza A viruses are the onlyinfluenza viruses known to cause flu pandemics, i.e., global epidemics of flu disease. A

pandemic can ocur when a new and very diferent influenza A virus emerges that both infects people and has the

ability to spread eficiently betwen people.

•Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: hemaglutinin (H) and

neuraminidase (N).Of al the influenza viruses that routinely circulate and cause ilnes in people, influenza A(H3N2)

virusestend to change more rapidly, both geneticaly and antigenicaly. Influenza A(H3N2) viruses have formed many

separate, geneticaly diferent clades in recent years that continue to co-circulate.

•Influenza type C infections generaly cause mild ilnes and are not thought to cause human flu epidemics.

•Influenza D viruses primarily afect catleand are not known to infect or cause ilnes in people.

Overview of Influenza (Flu) Viruses

Source: Literature research, Frost & Sulivan analysis

• Complications of flu can include bacterial pneumonia, ear infections, sinus infections and worsening of chronic medical conditions, such as congestive heart failure, asthma, or diabetes.

Fever	Fever

Runny nose or congestion
Runny nose or congestion

Cough
& sore throat	& sore throat

Body aches	Body aches

Fatigue

Chills & shivering

Headaches

Nausea, vomiting

& diarhea

Risk Factors

•Anyone can get flu (even healthy people), and

serious problems related to flu can hapen at

any age, but some people are at high risk of

developing serious flu-related complications

if they get sick.

•This includes people 65 years and older,

people of any age with certain chronic

medical conditions(such as asthma,

diabetes, or heart disease), pregnant women,

and children younger than 5 years.

ComplicationsSymptoms

Overview of Influenza (Flu)

Source: Literature research, Frost & Sulivan analysis

•Flu is a contagious respiratory ilnes caused by influenza viruses that infect the nose, throat, and sometimes

the lungs. It can cause mild to severe ilnes, and at times can lead to death. The best way to prevent flu is by geting

a flu vacine each year.

In principle, vaccination units should provide immunization services to all persons ≥6 months of age who are willing to be vaccinatedandhavenocontraindications.
Recommended Priority Groups for Vaccination

WHO and CDC Recomendations for Influenza Vacination

Resources: WHO, CDC, Frost & Sulivan Analysis

WHO

Pregnantwomenatanystageofpregnancy:

thereisevidenceofahighriskofotherserious

ilnesesasociatedwithinfluenzainpregnant

women.

Childrenaged6monthsto5years:theburden

ofseriousilnesishighforchildrenaged6-23

months,andsimilarlyhighforchildrenaged2-5

years,butlowerthantheburdenofilnesfor

childrenunder2yearsofage.

Elderly(65+):thereisgrowingevidencethat

vacinesarenotasefectiveinolderagegroups

astheyareinyoungeragegroups

Individuals with chronic diseases: Individuals

with specific chronic diseases are often also at

high risk for severe influenza-asociated ilneses,

and this group is often the primary target for

vacination

Health care workers: for this population,

vacination protects not only themselves from the

influenza virus, but also vulnerable patients

CDC

Recomended Priority Groups for Vacination

Medical personel: including clinical care

personel, public health personel, sanitary and

quarantine personel, etc.

Mega-event participants and suport staf

Vulnerable people and employes in places

where people gather, such as nursing homes,

long-term care facilities, welfare homes, etc.

Key populations: teachers and students in

childcare institutions, primary and secondary

schols, and detaines and staf of penal

institutions.

Other populations at high risk for influenza:

✓Homebound seniors age 60+

✓Infants 6-23 months of age

✓Children 2-5 years of age

✓Chronicaly il

✓Family members and caregivers of infants

younger than 6 months of age

✓Pregnant women or women planing to

become pregnant during the influenza season

CDC Recomends Influenza Vacination Doses

Resources: CDC, Frost & Sulivan Analysis

No Previous Influenza

Vacination

Previously Received 1+

Doses of Influenza Vacine

6 months -35

months of age:

•2 doses of IV3 or

IV4vacine at≥4

weks interval.

36 months -8

years:

•IV: 2 doses of

IV3 or IV4

vacine at ≥4

weksinterval;

•LAIV: 1 dose

9 years and older:

•IV: 1 dose of IV3

or IV4vacine;

•LAIV: 1 dose (9-

17 years only)

6 months to 35

months of age:

•1 dose of IV3 or

IV4vacine

36monthsofage

andolder:

•IV:1doseofIV3

orIV4vacine;

•LAIV:1dose(3-

17yearsonly)

•Inordertobeterguidetheworkofinfluenzapreventionandcontrolandvacineaplication,theCDCpreparedand

isuedthe”ChinaInfluenzaVacinePreventiveVacinationTechnicalGuidelines(2023-2024)”,inwhichrelevant

provisionsweremadeforthenumberofdosesofinfluenzavacinetobeadministered.

Note:(1) IV: Inactivated vacine, including spilt virion vacine and subunit vacine; (2) LAIV: Live-atenuated vacine

Influenza Vacine Clasification

Based on Valence

•In February 2012, the WHO recomended that seasonal influenza vacines include two B lineage strains, and from the

2013-2014 Northern Hemisphere flu season, it advised ading a fourth component (B Yamagata lineage) to suport the

development of quadrivalent vacines.

•Influenza vacines are clasified by the range of serotype coverage into trivalent vacines (including A/H1N1, A/H3N2,

and either B/Victoria or B/Yamagata lineages) and quadrivalent vacines (including A/H1N1, A/H3N2, B/Victoria, and

B/Yamagata lineages). Quadrivalent vacines ofer broader protection against B influenza viruses compared to trivalent

vacines.

Resources: WHO, Frost & Sulivan Analysis

+

A/H1N1A/H3N2B/VictoriaB/Yamagata

+

Trivalent Influenza Vacine

Quadrivalent Influenza Vacines

The Curent Serotype Voverage of Trivalent

and Quadrivalent Influenza Vacines

Influenza Vacine Clasification

Based on Vacination Population

Resources: Frost & Sulivan Analysis

•Acording to WHO and CDC recomendations, the influenza vacine should be administered to people over 6 months of

age, which can be subdivided into 6-35 months of age, 3 years of age and older, and the elderly for safety and

efectivenes reasons, and the coresponding vacines wil have some diferences in dosage.

Pediatric

Formulation

Adult

Formulation

Design Purpose

Target Group

Compared to adults, infants

and young children are more

susceptible to influenza

viruses, have a higher burden

of ilnes, are at higher risk for

serious complications, and

have a greater ned for

influenza vacines. For safety

reasons, pediatric doses of

influenza vacine require a

lower level of active antigen in

the vacine, but can be

administered at the same

concentration as adults.

Senior

Formulation

Infants and

todlers 6-35

months of age

People aged 3

years and above

Elderly

(Acording to WHO’s

recomended vacination

population, the age limit for the

elderly is 65 years and older,

while CDC’s age limit for the

elderly is 60 years and older.)

Influenza viruses can infect

people of al ages, and while

the vacines curently

available provide relatively

comprehensive coverage of

this population, there is a ned

for safer and more efective

vacines to met the neds of

the population.

Older adults have a greater

disease burden from influenza

and are at risk for serious

complications. However, due

to phenomena such as aging

of the imune system in the

elderly, the efectivenes of

existing vacines in the

elderly is not as satisfactory

as in adults, and influenza

vacine design for the elderly

is neded to met the

demand.

Note: Acording to the “Influenza Vacines: WHO Position Paper” (May 2022), curent quadrivalent and trivalent inactivated influenza vacines for individuals aged ≥3

years contain 15 micrograms of each HA subtype per dose. For children aged 6-36 months, the HA concentration is 7.5 micrograms or 15 micrograms per dose.

Influenza Vacine Clasification and Characterization

Besed on TechnologyType

Resources: Frost & Sulivan Analysis

Split-virus Influenza VacinesInactivated subunit vacine

Whole-virus Inactivated

Influenza Vacines

A whole-virus inactivated vacine

involves culturing the virus and

then inactivating it using heat or

chemicals. This type of vacine

contains complete virus particles.

A split-virus vacine involves

inactivating the virus and then

ading a lytic agent to disrupt its

lipid membrane. It contains

influenza virus nucleoprotein,

matrix protein, and other internal

proteins, along with surface

antigens.

An inactivated subunit vacine is

based on a split-virus vacine,

with membrane proteins HA

(hemaglutinin) and NA

(neuraminidase) isolated and

purified to obtain HA and NA

proteins.

•Influenza is a popular field of vacine research, with nearly a century of study on influenza vacines. They can be primarily

categorized into whole-virus inactivated influenza vacines, split-virus influenza vacines, and subunit influenza vacines.

Vacine

Description

Vacine

structure

HA (hemaglutinin)

NA (neuraminidase)

Split-virus

Vacine

mRNA Vacine

Inactivated

Subunit

Vacine

Live

Atenuated

Vacine

Recombinant

Vacine

Resources: Frost & Sulivan Analysis

Whole-virus

Inactivated

Vacine

•A whole-virus inactivated vacine involves culturing

the virus and then inactivating it with heat or

chemicals. This type of vacine contains various

antigenic proteins of the virus.

•A split-virus vacine involves inactivating the virus

and then ading a lytic agent to disrupt the viral lipid

membrane, alowing for beter purification of viral

antigens.

•Aninactivatedsubunitvacineisbasedonasplit-

virusvacine,withmembraneproteinsHAandNA

isolatedandpurifiedusingsuitablemethodsto

obtainHAandNAproteinsforvacinepreparation.

•A live atenuated vacine is produced using

atenuated strains obtained through virulence

variation or artificial selection, alowing it to mimic

viral infection without causing disease.

•Arecombinantvacineusesgeneticengineringto

insertDNAsequencesforviralantigensintohost

celsviaplasmids.Theantigensarethen

expresed,purified,andmadeintoavacine,often

usingthebaculovirus-insectcelsystem.

•AnmRNAvacinecontainsmRNAencoding

antigenproteins.Inthebody,itdirectlytranslates

intothecorespondingantigenprotein,bypasing

replicationandtranscription,tostimulateanimune

response.

•Simple and fast preparation method, high safety, long

history of aplication

•High inoculation dose, multiple inoculations required,

long production time

•Activates the imune system like a natural infection,

trigering a strong and long-lasting imune response

•Not suitable for people with weakened imune

systems

•Rapid and low-cost production, high safety and rapid

response to infectious disease pandemics

•Lack of long-term safety and eficacy studies, ned to

adres delivery isues

•High antigen purity, god safety

•Weak imunogenicity, ned to coperate with

coresponding adjuvant, ned to consider the

composition of the formulation

•Contains a single antigenic component, god safety,

few side efects

•Weak imunogenicity, ned to ensure the purity of the

antigen, ned to coperate with the apropriate

adjuvant

•Simple preparation method

•Antigenic composition not as simple as inactivated

subunit vacines, les safe than inactivated subunit

vacines

•Influenza is a popular field of vacine research, with nearly a century of study on influenza vacines. They can be primarily

categorized into whole-virus inactivated influenza vacines, split-virus influenza vacines, and subunit influenza vacines.

Vacine DescriptionVacine Characteristics

Influenza Vacine Clasification and Characterization

Besed on TechnologyType

• To ensure the quality of influenza vaccines, both theWHOand the Chinese Pharmacopoeia set standards for safety and efficacy indicators in finished product testing.TheWHOhasestablishedguidelinesforinactivatedinfluenzavaccines,includingwhole-virusinactivated,split-virus,andinactivatedsubunitvaccines.In contrast,theChinesePharmacopoeiaincludesonlywhole-virusinactivatedinfluenzavaccinesandsplit-virusinfluenzavaccines.

Key Indicators	Explanation of Key Indicators	WHO	Chinese Pharmacopoei
Key Indicators	Explanation of Key Indicators	including inactivated influenza vaccines (whole-virus inactivated influenza vaccine, split-virus influenza vaccine, and subunit influenza vaccine)	including whole-virus inactivated influenza vaccine and split-virus influenza vaccine
Hemaggluti nin Content	Key antigenic substances in influenza vaccines	• Each dose contains at least 15 μg hemagglutininofeachinfluenzavirus • In some countries, lower lower limits may be setbasedonclinicalexperience	• Whole-virus inactivated influenza vaccine: Each human dose is 0.5ml or 1.0ml, containing 15μg of HA from each influenza virus strain. • Split-virus influenza vaccine: Each human dose is 0.25ml, containing 7.5μgofHAfromeachinfluenzavirusstrain;or 0.5ml, containing15μgofHAfromeachstrain. • The HA content of each strain per dose should be no less than 80%ofthelabeledamount.
Endotoxin Content	A component of the cell wall of gram-negative bacteria that can cause a range of toxic reactions when it enters the body	• Allowable endotoxin levels are determined by individualstateregulatoryagencies	• Whole-virus inactivated influenza vaccine: Should not exceed 10 EUperdose. • Split-virusinfluenzavaccine:Shouldbelessthan20EUperml.
Protein Content	In addition to specific antigenic proteins, host cell proteins, protein A and other impurities may be present in the vaccine	• The total protein content shall not exceed six times the total hemagglutinin content of the vaccine as determined in the hemagglutinin contenttest.However,innocaseshalltheper persondoseexceed100μgofproteinpervirus strainandthetotalproteincontentexceed300 μgofproteinperpersondose	• Whole-virus inactivated influenza vaccine: Should not exceed 400μg/ml and must not be more than 4.5 times the total HA contentinthevaccine. • Split-virus influenza vaccine: Should not exceed 400μg/ml and must not be more than 4.5 times the total HA content in the vaccine.
Ovalbumin Content	Vaccines produced using chicken embryos may contain ovalbumin, an impurity in vaccine production	• Shouldbenohigherthan5μgperperson.	• Whole-virusinactivatedinfluenzavaccine:Shouldnotexceed250 ng/ml. • Split-virusinfluenzavaccine:Shouldnotexceed200ng/ml.

Influenza Vacine Safety and Eficacy Indicators

Resources: Literature Review, Frost & Sulivan Analysis

Key Indicators	Explanation of Key Indicators	WHO	Chinese Pharmacopoei
Key Indicators	Explanation of Key Indicators	including inactivated influenza vaccines (whole-virus inactivated influenza vaccine, split-virus influenza vaccine, and subunit influenza vaccine)	including whole-virus inactivated influenza vaccine and split-virus influenza vaccine
Other Residues Content	Includes free methanol, antibiotics and thiomersal used in vaccine production.	• Notspecified	• Antibiotics: The whole-virus inactivated influenza vaccine and split-virusinfluenzavaccineshouldnotexceed50ngperdose. • Thimerosal:Shouldnotexceed50μgperdoseinthewhole-virus inactivated influenza vaccine, and 100 μg/ml in the split-virus influenzavaccine. • Free methanol: Should not exceed 50 μg/ml in the split-virus influenzavaccine.

Influenza Vacine Safety and Eficacy Indicators

Resources: Literature Review, Frost & Sulivan Analysis

30.8

57.7

83.0

78.7

70.5

75.4

Lot Release of Influenza Vacinein China, 2019-2024

•TheinfluenzavacinemarketinChinahasgrownsignificantlyfrom2019to2021,andecreasedinextwoyears.Thetotal

numberoflotreleaseincreasedfrom30.8milionin2019to83.0milionin2021,andslightlydecreasedto70.5milionin2023.And

in2024itroseagainto75.4milion.TheCAGRfrom2019to2024is19.6%.

•China’squadrivalentinfluenzavacinemarkethasgrownsignificantly.Thetotalnumberoflotreleaseincreasedfrom9.7milionin

2019to46.6milionin2024,ataCAGRof36.8%.

Lot Release of InfluenzaVacine in China , 2019-2024

PeriodCAGR

2019-202419.6%

Milion

Source: Expert interview, NIFDC, Frost & Sulivan analysis

1.8
15.7 2.9

1.4
14.3 2.7

1.1
12.9 2.5

0.9
11.5 2.3

0.7
10.0

1.0
9.0

0.5
5.3

•The influenza vacine market in China has also grown significantly from RMB2.0 bilion in 2019 to RMB7.0 bilion in 2024, at a

CAGR of 28.7%. The influenza vacine market in China is estimated to further increase to RMB20.5 bilion in 2033, at a CAGR of

12.6% from 2024 to 2033.

–

0.01 0.02 0.1

0.4 0.7

0.9 1.2

1.5 1.8

2.0 2.3

2.5 2.7 2.9

2.0

9.3

8.1

6.1

6.4

6.8

7.6

8.7

0.5

0.3

0.2

0.3

0.4

0.5

0.7

0.9

2.0

5.8

10.1 9.9

8.8

7.0

7.6

8.4

9.4

10.9

12.7

14.6

16.5

18.5

20.5

2019202020212022202320242025E2026E2027E2028E2029E2030E2031E2032E2033E

subunit vacinesplit virion vacineother technical route

China Influenza Vacine Market Production Value, Separated by

Technical Route, 2019-2033E

China Influenza Vacine Market Production Value, 2019-2033E

Unit: Bilion RMB

Source: Expert interview, NIFDC, Frost & Sulivan analysis

Period

CAGR

Subunit vacineSplit virion vacineOther technical routesTotal

2019-2024-25.3%-28.7%

2024-2033E18.0%11.0%26.3%12.6%

12.6
7.8

11.5
6.9

10.5
6.1

9.4
5.2

8.3
4.4

7.8

8.0

7.3
3.6

5.3

5.8

0.8

1.5

2.2 1.9

1.1

2.0 2.3 2.6

3.1

3.6

1.2

4.3

7.7

5.0

6.4

2.0

5.8

10.1 9.9

8.8

7.0

7.6

8.4

9.4

10.9

12.7

14.6

16.5

18.5

20.5

2019202020212022202320242025E2026E2027E2028E2029E2030E2031E2032E2033E

TrivalentQuadrivalent

China Influenza Vacine Market Production Value, Separated by Tri-

and Quadri-valent, 2019-2033E

China Influenza Vacine Market Production Value, 2019-2033E

Unit: Bilion RMB

Source: Expert interview, NIFDC, Frost & Sulivan analysis

Period

CAGR

TrivalentQuadrivalentTotal

2019-202421.5%32.6%28.7%

2024-2033E16.1%10.9%12.6%

•The influenza vacine market in China has grown to RMB7,007 milion in 2024, and it wil be reach to RMB20,468.4 milion in

2033, with a CAGR of 12.6% from 2024 to 2033.

2.1
0.8

1.9
0.8

1.8
0.7

1.6
0.7

1.4
0.6

1.2
0.5

1.1
0.4

0.9
0.3

–

0.01 0.02

0.1

-0.1

0.2

–

0.4

0.6

0.7

-0.01 0.02

0.1

0.4

0.7

0.9

1.2

1.5

1.8

2.0

2.3

2.5

2.7

2.9

2019202020212022202320242025E2026E2027E2028E2029E2030E2031E2032E2033E

TrivalentQuadrivalent

China Subunit Influenza Vacine Market Production Value,

Separated by Tri-and Quadri-valent, 2019-2033E

China Subunit Influenza Vacine Market Production Value, 2019-2033E

Unit: Bilion RMB

Source: Expert interview, NIFDC, Frost & Sulivan analysis

Period

CAGR

TrivalentQuadrivalentTotal

2019-2024-

2024-2033E30.9%15.2%18.0%

•The subunit influenza vacine market in China has grown to RMB 0.7 bilion in 2024. With the aproval of more subunit influenza

vacine products in the future, it wil be able to drive market to RMB 2.9 bilion in 2033, with a CAGR of 18.0% from 2024 to2033.

Type	Brand Name (Generic Name)	Technical Route	Company	FDA approval date*	Age Coverage

Marketed Influenza Vacines in global market (1)

Trivalent

FLUVIRINInactivated, subunit

Seqirus

19884 years of age and older

AFLURIASplit Virion2007/096 month of age and older

AgrifluInactivated, subunit2009/1118 years of age and older

FlucelvaxInactivated, subunit2012/116 month of age and older

FLUADInactivated, subunit2015/1165 years of age and older

FluzoneSplit Virion

Sanofi

19806 month of age and older

FluzoneHigh-DoseSplit Virion2009/1265 years of age and older

FluzoneIntradermalSplit Virion2011/0518-64 years of age

FlublokRecombinant, subunit2013/0118 years of age and older

FluarixSplit Virion

GSK

2005/086 month of age and older

FluLavalSplit Virion2006/106 month of age and older

FluMistLive AtenuatedAZ2003/062-49 years of age

Note: The aproval date is the time when the vacine was first aproved, without considering the expansion of the age group of the vacinated population

By end of July 21

, 2025

Source：FDA, Frost & Sulivan

Type	Brand Name (Generic Name)	Technical Route	Company	FDA approval date*	Age Coverage

Marketed Influenza Vacines in global market (2)

Quadrivalent

Flucelvax QuadrivalentInactivated, subunit

Seqirus

2016/056 month of age and older

Afluria QuadrivalentSplit Virion2017/076 month of age and older

FluadQuadrivalentInactivated, subunit2020/0265 years of age and older

FluzoneQuadrivalentSplit Virion

Sanofi

2013/66 month of age and older

FluzoneIntradermal

Quadrivalent

Split Virion2014/1218-64 years of age

FlublokQuadrivalentRecombinant, subunit2016/1018 years of age and older

FluzoneHigh-Dose

Quadrivalent

Split Virion2019/1165 years of age and older

Fluarix QuadrivalentSplit Virion

GSK

2012/116 month of age and older

FlulavalQuadrivalentSplit Virion2013/086 month of age and older

FluMistQuadrivalentLive AtenuatedAZ2003/072-49 years of age

Note: The aproval date is the time when the vacine was first aproved, without considering the expansion of the age group of the vacinated population

By end of July 21

, 2025

Source：FDA, Frost & Sulivan

Type	Generic Name	Technical Route	Company	Clinical Stage	FPD	Age Coverage	Location

Source: CclinicalTrials.gov, Frost & Sulivan

Competitive landscape of Influenza Vacines in global market

Name

Trivalent

GSK4382276AmRNAGSKI2024/05/28

Adults 18 Years of Age

and Older

PF-07845104mRNAPfizerI/I (completed)2024/05/31

Adults 18 Years of Age

and Older

Quadrivalent

mRNA-1010

mRNAModerna

I2024/09/19Adults ≥50 Years of AgeGlobal

mRNA-1020I/I (completed)2022/04/18

Adults 18 Years of Age

and Older

mRNA-1030I/I (completed)2022/04/18

Adults 18 Years of Age

and Older

SP0237mRNASanofi I2024/04/12

Adults 18 Years of Age

and Older

US, Puerto Rico,

Honduras

OVX836

Non-VLP

nanoparticles

OsivaxI (completed)2024/09/03

Adults 20 to 69 Years of

Age

Belgium

KBP-V001RecombinantKBioI (completed)2020/06/19

Adults 18 to 49 Years of

Age

PentavalentmRNA-1011mRNAModernaI/I (completed)2023/04/24

Adults 50 to 75 Years of

Age

Hexavalent

mRNA-1012mRNAModernaI/I (completed)2023/04/24

Adults 50 to 75 Years of

Age

-mRNASanofiI/I2024/12/20

Adults 50 Years of Age

and Older

US, Australia

Not DiscloseUFluA

Non-VLP

nanoparticles

Emergent

BioSolutions

I (completed)2021/12/13

Adults 18 to 45 Years of

Age

Australia

By end of July 21

, 2025

Type	Brand Name (Generic Name)	Technical Route	Company	NMPA approval date1	Age Coverage	End-user Price2	Market Share3 (2024)

Marketed Influenza Vacines in China(1)

unknown-

Whole Virion

Inactivated

Lanzhou institute of biological

products

（兰州生物制品研究所）

2000NANA-

Trivalent

英扶宁Split Virion2005/02

6 months of age and

older

NA-

-Split Virion

CuroVax

（康润生物）

2005/03

3 years of age and

older

NA-

Anflu

(安尔来福)

Split Virion

Sinovac

（科兴）

2007/01

6 months of age and

older

52.5 (0.25ml)

80 (0.5ml)

10.0%

Influenza

vacine

Split Virion

Shanghai institute of biological

products

（上海生物制品研究所）

2007/05

6 months of age and

older

31 (0.25ml)

58 (0.5ml)

2.5%

YUGANING

(御感宁)

Split Virion

TOYOUVAX

（天元生物）

2007/06

6 months of age and

older

68 (0.25ml)

88 (0.5ml)

1.8%

适普利尔Split Virion

Changchun institute of biological

products

（长春生物制品研究所）

2004/09

6 months of age and

older

31 (0.25ml)

50 (0.5ml)

6.8%

Influenza

vacine

Split Virion

Hualan Biological Bacterin

（华兰生物）

2008/04

6 months of age and

older

31 (0.25ml)

53 (0.5ml)

3.8%

Influenza

vacine

Split Virion

Fosun Apexvac

（复星雅立峰）

2009/06

6 months of age and

older

60.5 (0.25ml)

80.5 (0.5ml)

7.0%

FLU-K

(孚洛克)

Subunit

ZHONGYIANKE biotech

（中逸安科）

2010/04

3 years of age and

older

168 (0.5ml)0.5%

-Split Virion

AIM

（艾美疫苗）

2012/11

3 years of age and

older

NA-

VAXIGRIP

(凡尔灵)

Split Virion

Sanofi Pasteur Biological

Products

2013/06

6 months of age and

older

55 (0.25ml)

70 (0.5ml)

4.8%

Influenza

vacine

Split Virion

Adimune

（国光生物）

2015/10

3 years of age and

older

135.5 (0.5ml)-

感雾live atenuated

BCHT

（百克生物）

2020/023-17 years of age298 (0.2ml)0.9%

Source：NMPA, Frost & Sulivan

Type	Brand Name (Generic Name)	Technical Route	Company	NMPA approval date*	Age Coverage	End-user Price*	Market Share (2024)

Marketed Influenza Vacines in China(2)

Quadrivalent

Influenza vacine,

quadrivalent

Split Virion

Hualan Biological

Bacterin

（华兰生物）

2018/066 months of age and older

128 (0.25ml)

88 (0.5ml)

20.1%

迪福赛尔Split Virion

GDK biological

technology

（金迪克生物）

2019/053 years of age and older88 (0.5ml)3.5%

Influenza vacine,

quadrivalent

Split Virion

Changchun institute of

biological products

（长春生物制品研究所）

2020/033 years of age and older95 (0.5ml)2.9%

Influenza vacine,

quadrivalent

Split Virion

Wuhan institute of

biological products

（武汉生物制品研究所）

2020/043 years of age and older88 (0.5ml)4.8%

Influenza vacine,

quadrivalent

Split Virion

Sinovac

（科兴）

2020/063 years of age and older88 (0.5ml)13.8%

Influenza vacine,

quadrivalent

Split Virion

Shanghai institute of

biological products

（上海生物制品研究所）

2021/036 months of age and older91.5 (0.5ml)9.5%

安定伏Split Virion

Adimune

（国光生物）

2022/023 years of age and older205.5 (0.5ml)0.5%

VaxigripTetra

（凡尔佳）

Split Virion

Sanofi Pasteur Biological

Products

2023/026 months of age and older128 (0.5ml)4.3%

Influenza vacine,

quadrivalent

Split Virion

ZFSW

（智飞生物）

2025/033 years of age and olderNA-

Influenza vacine,

quadrivalent

Split Virion

Fosun Apexvac

（复星雅立峰）

2025/063 years of age and olderNA-

Influenza vacine,

quadrivalent

Split Virion

TOYOUVAX

（天元生物药业）

2025/07NANA-

慧尔康欣Subunit

Ab&bBiotechnology

（中慧元通）

2023/053 years of age and older319 (0.5ml)2.4%

Source：NMPA, Frost & Sulivan

Note:

1.The aproval date is the time when the vacine was first aproved, without considering the expansion of the age group of the vacinated population;

2.The end-user price is determined by the median of wining bid prices in provinces with publicly disclosed data in2024;

3.The market share was calculated by Production volume;

4.By end of July 21

, 2025

Type	Technical Route	Company	Clinical Stage	FPD*	Age Coverage

Competitive Landscape of Influenza Vacines in China

Source: CDE, Frost & Sulivan

Trivalent

Subunit

Ab&bBiotechnology

（中慧生物）

NDA2024/9/193 years of age and older

NDA2024/10/16-35 months of age

Live atenuated

BCHT

（百克生物）

NDA2024/4/243-59 years of age

Split Virion

ZFSW

（智飞生物）

NDA2024/10/243 years of age and older

NDA2024/11/26-35 months of age;

Split Virion

Chengdabiotechnology

（成大生物）

NDA2025/3/21NA

Split Virion

Olymvax

（欧林生物）

I2025/1/236 months of age and older

Split Virion

PeisenBiotechnology

（培森生物）

I (completed)2022/3/293 years of age and older

Quadrivalent

Subunit

Ab&bBiotechnology

（中慧生物）

NDA2024/6/286-35 months of age

Subunit

Changchun institute of

biological products

（长春生物制品研究所）

I2024/04/283 years of age and older

Split Virion

CuroVax

（康润生物）

NDA2024/3/223 years of age and older

I2024/4/36-35 months of age

Split Virion

ZFSW

（智飞生物）

NDA2024/9/306-35 months of age

Split Virion

Wuhan institute of biological

products

（武汉生物制品研究所）

NDA2024/11/143 years of age and older

Split Virion

BioKangtai

（康泰生物）

NDA2024/11/223 years of age and older

Split Virion

Chengdabiotechnology

（成大生物）

NDA2025/1/243 years of age and older

*Note: The dates for products in NDA stage are the dates handled by CDE

By end of July 21

, 2025

Type	Technical Route	Company	Clinical Stage	FPD*	Age Coverage

Competitive Landscape of Influenza Vacines in China

*Note: The dates for products in NDA stage are the dates handled by CDE

By end of July 21

, 2025

Quadrivalent

Split Virion

Sinovac

（科兴）

I(completed)2023/96-35 months of age

Split Virion

WALVAX

（沃森生物）

I2024/103 years of age and older

Split Virion

ZFSW

（智飞生物）

I/I2025/1Adults 18 Years of Age and Older

Split Virion

Olymvax

（欧林生物）

I2025/16 months of age and older

Split Virion

Hygiea Biotech

（海基亚生物）

I2020/10

6-35 months of age; 3 years of age

and older

I2025/43 years of age and older

Split Virion

GDK biological technology

（金迪克）

NDA2025/76-35 months of age

Source: CDE, Frost & Sulivan

Growth Drivers and Future Trends of the Chinese Influenza Vacine

Market

•Influenza afects individuals of al ages, especialy infants, children and the elderly, necesitating

widespread imunization. The China CDC advises anual vacinations for al individuals aged six

months and above who are wiling and have no contraindications. The target population for influenza

vacines is huge and the market demand is high. As the imune protection generated by influenza

decrease over time and the frequent emergence of influenza virus mutations may result in mismatch

betwen the vacine strain and the prevalent virus strain, it is necesary to receive anual vacination

for best protection. China CDC also recomends vacination of one to two doses to generate a

suficient amount of antibodies. The anual and multi dose vacination of influenza vacines has

expanded market demand for vacines and driven market development.

Increased market

demand

Favorable policies

•Though influenza vacines are not included in China’s national imunization program, several regions

have initiated fre vacination schemes for certain demographics, bosting public vacination rates. For

instance, Beijing ofers fre vacines to residents over 60, students and other key groups, while

Zhejiang and Shenzhen have similar initiatives that ofer fre vacines to the elderly. These policies

increase public wilingnes to vacinate, promoting market growth.

•In recent years, in order to improve the vacination rate, the country has introduced various policies to

promote the popularization of influenza vacines. The “14th Five Year Plan for National Health （《“十

四五”国民健康规划》）” released by the State Council in April 2022 and the “Notice on Doing a God

Job in the Prevention and Control of Influenza in the 2021-2022 Epidemic Season（《关于做好2021-

2022年六星级流感防控工作的通知》）” isued by the Comprehensive Group of the State Council Joint

Prevention and Control Mechanism in October 2021 clearly state that: ①Encourage places with

conditions to implement fre vacination, improve the vacination rate of influenza vacines, and reduce

the ocurence of clustered influenza epidemics; ②Reasonably plan or ad an influenza vacination

unit, and make overal arangements for the vacination of COVID-19 vacine, influenza vacine and

other routine vacines; ③Information management of vacination data.

Source: Frost & Sulivan

Growth Drivers and Future Trends of the Chinese Influenza Vacine

Market

•The aproval of the Company’s quadrivalent subunit influenza vacine, which is the first marketed

quadrivalent subunit influenza vacine in China, in May 2023 represents a significant advancement,

adresing a domestic gap with its high safety and targeted protection. Inspired by mRNA COVID-19

vacine suceses, there has ben a notable increase in investment in developing mRNA vacines and

other diverse vacine types, providing more choices, beter protection with enhanced safety to target

populations, and thus bosting market adoption.

The number of

players is increasing,

production capacity

is expanding, and

new vacines are

gradualy emerging

Source: Frost & Sulivan

•Due to the impact of the COVID-19, the number of influenza cases in 2020 and 2021 is low, resulting in

a low demand for influenza vacination. However, the COVID-19 has greatly strengthened the residents’

awarenes of influenza prevention and control and their wilingnes to vacinate. At the same time, in

September 2023, the Chinese CDC released the “Technical Guidelines for Influenza Vacination in

China (2023-2024) （《中国流感疫苗预防接种技术指南（2023—2024）》）”, which pointed out that

anual influenza vacination is the most economical and efective measure to prevent influenza.

Require al disease control centers to actively organize scientific popularization, health education, risk

comunication, etc., guide the public to scientificaly understand and prevent influenza, enhance

protection awarenes and health literacy, and gradualy improve vacine coverage for key populations

The epidemic drives

the recovery of

demand for

influenza vacines

1	Overview of the human vaccine market

1.1	Overview of the vaccine industry background

1.2	Classification of vaccines by technical route

1.3	Overview of the Global Vaccine Market

1.4	Overview of the China Vaccine Market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

Risk Factors

Hypertension

Overview ofPneumococal Disease（PD）

•Pneumococal disease（PD）including a wide range of diseases caused by Streptococus pneumoniae (Spn).Spn

infections range from ear and sinus infections to pneumonia and blodstream infections.

IPD is more severe than NIPD

and ocur in major organs or in

a person’s blodstream.

Including：

•Bacteremia

•Sepsis

•Meningitis

•Pneumonia

•Osteomyelitis

•Septic arthritis

Invasive

Pneumococal

Disease(IPD)

NIPD ocur outside the

major organs or blodstream.

Streptococus pneumoniae

can spread from the nose

and throat to the uper and

lower respiratory tracts. The

bacteria can cause:

•Otitis media

•Bronchitis

•Nasosinusitis

Non-invasive

Pneumococal

Disease (NIPD)

AgeDiabetes

Melitus

Children

（under 5）

Smoking…

Cardiovas

Cular

Disease

Nephropa

-thy

…

Midle Ear

Efusion;

Ear Pain

Chest Pain,

Acelerated

Heartbeat

Cough

Fever

Pain，Sweling

around The

Cheks

Symptoms

Source: Frost & Sulivan Analysis

Infection
• Infection is primarily through Streptococcus pneumoniae in respiratory droplets. There are many healthy, asymptomatic carriers of the bacteria, but no animal hosts or insect vectors. • Bacteria can be spread by airborne droplets, for example, when an infected person coughs or sneezes. Bacteria are not spread through contaminated food or water.

Mechanism of infection

•Streptococus pneumoniae often

colonizes the nasopharynx, and from

the nasopharynx, pneumococi can

spread directly through the airway to

the lower respiratory tract, causing

pneumonia, or to the sinuses or

midle ear, causing disease.

•Bacteria may also penetrate the

epithelial cel surface, leading to

localized infection or bacteremia.

Pleura and meninges can be

infected through local transmision

of infection or bacteraemia.

•Invasive Pneumococal Disease is

an infection evidenced by the

isolation of bacteria from a normaly

sterile site (e.g., blod, cerebrospinal

fluid, or pleural cavity), which is

caused by invasion of respiratory

epithelium.

•Streptococus pneumoniae（Spn）is the leading cause of comunity-acquired pneumonia.The incidence of pneumococal

pneumonia is highest in individuals of extreme age and with comorbid .

•There are more than 90 known serotypes of Streptococus pneumoniae. Distribution of serotypes causing disease varies with time and

age, disease syndrome, disease severity, geographic region, and presence of antimicrobial genes. Prior to the introduction of

Streptococus pneumoniae conjugate vacine (PCV) by WHO in diferent regions, 6-11 serotypes acounted for more than 70% of al

invasive pneumococal diseases (IPD).

（Streptococus pneumoniae）

Source: Frost & Sulivan Analysis

Overview of Streptococus Pneumoniae（Spn）

Pneumococal Disease Treatment and Prevention

•In the clinical treatment of pneumococal disease, the primary consideration is the selection of a sensitive antibiotic. However,

Streptococus pneumoniae (Spn) can develop resistance to comonly used antibiotics, significantly increasing the dificulty of

treatment.

•With the growing isue of pneumococal antibiotic resistance and the increasing prevalence of pneumococal disease

complications, the use of pneumococal vacines to prevent pneumococal disease has become increasingly necesary and

urgent.

•With the introduction of widespread pneumococal vacination, resistant Streptococus

pneumoniae (Spn) strains have decreased in some developed regions. However, in

many Asian countries where antibiotics are widely used, resistant clones spread

extensively, and vacine coverage is low, the isue of Spnresistance remains severe.

•Furthermore, in China, the incidence of cros-resistance and multidrug resistance in Spn

to comonly used antibiotics is high. Data from the Asia-Pacific region’s Pathogen

Resistance Monitoring Network in 2012 showed that the overal multidrug resistance rate

of Spnin Asia was 59.3%, while in China, this rate was as high as 83.3%.

•The mortality rate of invasive

pneumococal disease in children is

very high. In low-and midle-income

countries, sepsis can have a mortality

rate of up to 20%, while meningitis can

reach as high as 50%.

•Among children who survive

pneumococal meningitis, 24.7%

experience long-term neurological

sequelae, such as hearing los,

intelectual disability, motor

abnormalities, and seizures.

Morbidity and Mortality

Afterefects

Antimicrobial Drug Resistance

•Curently, in the clinical treatment of pneumococal disease (PD), antibiotic therapy is

the first choice. However, Streptococus pneumoniae (Spn) has developed significant

resistance to comonly used antibiotics, such as penicilins, macrolides, quinolones,

cephalosporins, and TMP-SMX, which has become a serious global isue.

Disease treatment

Vacine Aplications

•The use of pneumococal vacines efectively reduces bacterial resistance and prevents S.

pneumoniae-related diseases. Particularly, the aplication of conjugate vacines has shown

significant and consistent efectivenes in preventing pneumococal disease in children, with

the safety of the vacines also being further confirmed.

Resources: WHO, Literature Review, Frost & Sulivan Analysis

Unit: Billion RMB 19.7 18.1 16.5 14.9 13.7 13.3 11.8 10.5 10.3 9.2 9.1 8.5 8.2 7.5 5.1
2019 2020 2021 2022 2023 2024 2025E 2026E 2027E 2028E 2029E 2030E 2031E 2032E 2033E

China Pneumococal Vacine Market Production Value, 2019-2033E

•ThepneumococalvacinemarketinChina,intermsofproductionvalueincreasedfromRMB5.1bilionin2019toRMB7.5bilionin

2024,ataCAGRof8.0%.Thetotalnumberoflotreleaseincreasedfrom14.2milionin2019to16.6milionin2024.Itisexpected

tofurtherincreasetoRMB19.7bilionin2033,ataCAGRof11.3%from2024to2033.

China Pneumococal Vacine Market Production Value, 2019-2033E

Source: Expert interview, NIFDC, Frost & Sulivan analysis

PeriodCAGR

2019-20248.0%

2024-2033E11.3%

Type	Brand Name (Generic Name)	Technical Route	Company	NMPA approval date*	Age Coverage

Marketed Pneumococal Vacinesin China

23-valent

PNEUMOVAX

（纽莫法）

Polysacharide

MSD2010/02

50 years of age and older; ≥2 years

who are at increased risk

沃朵菲

WALVAX

（沃森生物）

2017/03≥2 years who are at increased risk

维民菲乐

MINHAI

（民海生物）

2018/08≥2 years who are at increased risk

惠益康

Chengdu institute of biological

products

（成都生物制品研究所）

2020/07≥2 years who are at increased risk

23-valent Pneumococal

Polysacharide Vacine

Sinovac

（科兴）

2020/12≥2 years who are at increased risk

优威克

ZFSW

（智飞生物）

2023/08≥2 years who are at increased risk

13-valent

Prevnar 13

Polysacharide conjugate

Pfizer2016/106 weks through 5 years of age

维民菲宝

MINHAI

（民海生物）

2021/096 weks through 5 years of age

Weuphoria

（沃安心13）

WALVAX

（沃森生物）

2019/126 weks through 5 years of age

优佩欣

Cansino

（康希诺）

2025/066 weks through 5 years of age

Note: The aproval date is the time when the vacine was first aproved, without considering the expansion of the age group of the vacinated population

By end of July 21

, 2025

Source：NMPA, Frost & Sulivan

Type	Technical Route	Company	Clinical Stage	FPD	Age Coverage

Competitive Landscape of Pneumococal Vacines in China

By end of July 21

, 2025

Source: CDE, Frost & Sulivan

13-valent

Polysacharide

conjugate

Lanzhou Institute of

Biological Products

（兰州生物制品研究所）

NDA2023/3/162 months through 5 years of age (at least 6 weks of age)

(completed)

2016/7/42 months through 59 years of age (at least 6 weks of age)

AIM

（艾美疫苗）

NDA2024/11/152 months through 5 years of age (at least 6 weks of age)

FosumAdgenvax

（复星安特金）

I2022/5/72-3 months of age (at least 6 weks of age)

I2020/4/212 months of age and older (at least 6 weks of age)

SinoVac

（科兴）

I2023/10/192 months through 5 years of age (at least 6 weks of age)

I2022/8/302 months of age and older (at least 6 weks of age)

KunliBiopharmaceutical

（坤力生物）

I2021/7/272 months through 59 years of age (at least 6 weks of age)

MicrovacBiotech

（微超生物）

I2022/3/242 months through 49 years of age (at least 6 weks of age)

BravoVax, chengda

（博沃生物/辽宁成大）

I2022/10/282 months of age and older (at least 6 weks of age)

Chengdu Institute of

Biological Products

（成都生物制品研究所）

I2023/3/232 months through 59 years of age (at least 6 weks of age)

Type	Technical Route	Company	Clinical Stage	FPD	Age Coverage

Competitive Landscape of Pneumococal Vacines in China

By end of July 21

, 2025

Source: CDE, Frost & Sulivan

23-valentPolysacharide

Lanzhou Institute of

Biological Products

（兰州生物制品研究所）

(completed)

2015/12/242 years of age and older

AimeiVacinBioPharm

（艾美卫信）

I2023/8/12 years of age and older

Ab&bBiotechnology

（中慧元通生物）

(completed)

2020/9/82 years of age and older

20-valent

Polysacharide

conjugate

MINHAI

（民海生物）

I2025/3/212 months through 5 years of age

I2024/11/202 months through 59 years of age

InovaxBiotech

（万泰沧海生物）

I2023/3/136 weks of age and older

MicrovacBiotech/JUWEI

BIO

（微超生物/聚微生物）

I2023/4/32 months through 55 years of age (at least 6 weks of age)

Pfizer

（辉瑞）

I2025/5/76 weks through 49 years of age

I2025/6/1850 years of age and older

15-valent

Polysacharide

conjugate

ZFSW

（智飞生物）

NDA2025/6/53 months through 5 years of age

(completed)

2019/6/46 weks of age and older

26-valent

Polysacharide

conjugate

ZFSW

（智飞生物）

I/I2024/8/202 months of age and older (at least 6 weks of age)

Not Aplicable

Protein-based

pneumococal

vacine

Cansino

（康希诺）

(completed)

2019/9/618-49 years of age

I2022/11/950 years of age and older

Type	Technical Route	Company	Clinical Stage	FPD	Age Coverage

Competitive Landscape of Pneumococal Vacines in China

By end of July 21

, 2025

Source: CDE, Frost & Sulivan

24-valent

Polysacharide

conjugate

Reinovax

（瑞宙生物）

I2024/4/1518 years of age and older

I2024/4/152 months through 17 years of age (at least 6 weks of age)

KunliBiopharmaceutical

（坤力生物）

I/I

(completed)

2022/2/1818 years of age and older

FosumAdgenvax

（复兴安特金）

I2025/5/282 months of age and older (at least 6 weks of age)

SinoVac

（科兴）

I2024/8/132-17 years of age

I2025/1/232-23 months of age

Ib/I2025/6/1318 years of age and older

Growth Drivers and Future Trends of the Chinese Pneumococal

Vacines market

•Asageincreases,theriskofpneumococaldiseasealsoincreasesamongthelderly

populationaged65andabove.In2023, By2023,thepopulationaged65andabovein

Chinahasreached216.8milion,andisexpectedtogrowto286.0milionby2032.Withthe

developmentoftheagingtrendofChina’spopulationandthecontinuousimprovementof

percapitadisposableincome,thedemandforpneumococalvacine(especialy23valent

pneumococalpolysacharidevacine)wilgradualyincrease,andthemarketscaleof

pneumococalvacineisexpectedtocontinuetoexpand.

Increased risk

among the elderly

•InmanyregionsofChina,pneumococalvacinesarestilnotcoveredbyimunization

programandwithrelativelylowvacinationrates.DuetotheseriousilnescausedbySpn,

theWHOrecomendsthatalcountriesincludePCVintheirimunizationschedules,and

theUSCDCalsorecomendsthathepublicreceivevacines.Basedontheincreasing

healthawarenesoftheChinesepeople,thedemandforpreventivemedicalcarewilalso

increase.ThevacinationrateofpneumococalvacineinChinawilgradualyincrease,

thusthemarketsizeisexpectedtoexpand.

The vacination rate

of pneumococal

vacine has

increased

Source: Frost & Sulivan

•Multivalentpneumococalvacinesadresabroaderarayofpneumococalserotypes

andhighervalentvacinescanpreventmorepneumococalserotypesandthushavebeter

preventivefects.PCV7hasbengradualyreplacedbyPCV13.Meanwhile,PCV24is

beingdevelopedandsomePCV24candidateshaventeredtheclinicalstage.Theserotype

coveragewilikelyexpandfurtherwiththecontinuousdevelopmentofnewpneumococal

vacines.

Expansion of

serotype coverage

Future Trends of Chinese Pneumococal Vacines Market

•Atpresent,the13valentPCVscurentlyunderdevelopmentinChinahasexpandeditscope

ofaplicationtoawiderpopulation.Someclinicaltrialshavestudiedhealthyindividualsaged

2months(minimum6weks)to59yearsold,whilethetwo24valentpneumococal

polysacharideconjugatevacinescurentlyunderdevelopmentareaplicabletoindividuals

aged18yearsandabove.Withtheacumulationofrichexperienceinthexperimental

population,thescopeofaplicationofpneumococalpolysacharideconjugatevacinewil

continuetoexpand.

The scope of

aplication for

pneumococal

vacine expands

•Priorto2019,Pfizer’sPrevnar13wastheonly13-valentPCVaprovedandcurentlyonsale

worldwide.Athendof2019,thedomesticalyproduced13-valentPCVbrokePfizer’simport

monopolyandwaslaunchedintheChinesemarketin2020.Withthesuportofnational

policiesandtheinfluxofalargenumberofoverseasreturneswithcuting-edgetechnology,

domesticmanufacturershavebeguntogradualybreakthemonopolyofmultinational

companies.Atpresent,Chinahastwodomesticalyproduced13-valentPCVsonthemarket,

fivedomesticalyproduced23-valentPSVs.Thenumberofdomesticalyproducedvacines

wilgradualyincreaseinthefuture.

An increase in

domesticaly

produced

pneumonia

vacines

Source: Frost & Sulivan

1	Overview of the human vaccine market

1.1	Overview of the vaccine industry background

1.2	Classification of vaccines by technical route

1.3	Overview of the Global Vaccine Market

1.4	Overview of the China Vaccine Market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

•RespiratorySyncytialVirus(RSV)belongstothePneumovirusgenusoftheParamyxoviridaefamily.Basedonviralstrain

diferences,humanRSVhastwoprimaryantigenicsubtypes(AandB),mainlydeterminedbyantigenicdriftand

duplicationsintheRSV-Gsequence,alongwithwhole-genomesequencevariations,includingdiferenceswithinthe

RSV-Fsequence.

•AlthoughRSVwasdiscoveredasearlyas1955,itstructurehasonlybenelucidatedinthepastdecade.

Morphology and Structure of RSV and Key Timeline ofVirus

Research

Firstdiscoveredin

chimpanzes.

Firstdiscovered

inhuman

Thefirstformalin-

inactivatedRSVvacine

Thefirstpalivizumab

aprovedintheU.S.forthe

treatmentofRSVinfection

ALN-RSV01becamethe

firstsiRNAtherapy

aprovedforclinicaltrials.

Thestructureofthe

prefusionFproteinofRSV

hasbenelucidated.

The structure of the postfusionF

protein and polymerase complex of

RSV has ben elucidated.

TheRSVvacinehasbendesignated

bytheWHOasoneofthehighest

priorityvacinesforglobaldevelopment.

IGF1Rwasidentifiedasa

receptorforRSVentryinto

thehost.

Moderna’smRNAvacine

enteredPhaseIclinical

trials.

ThewholegenomeofRSVisegmentedinto10genes,encoding3non-structural

proteinsand8structuralproteins.Amongthestructuralproteins,threarelocatedonthe

virusurface:

The morphology and structure of

RSV

Key Timeline in Respiratory Syncytial Virus Research

✓Fusionglycoprotein(F):ItanchoredtotheRSVmembranesurfacethroughits

transmembranedomain.IntercelularAdhesionMolecule-1(ICAM-1),atypeIglycoproteinin

theimunoglobulinsuperfamily,facilitatesRSVentryandinfectioninhumanepithelialcels

bybindingtotheFglycoprotein.TheFproteinexistsintwoconformations:prefusionFand

postfusionF.WhenthevirusfuseswiththecelviatheFprotein,theunstableprefusionF

undergoesaconformationalchangeintothestablepostfusionF.

✓Smalhydrophobicprotein(SH):Formingapentamericionchanelandisthoughtobe

asociatedwithdelayedapoptosisofinfectedcels.

✓Atachmentglycoprotein(G): Primarilyfunctionstobindtheviralparticletothecelsurface

byinteractingwithadhesionmoleculesonthehostcel.

资料来源：WHO，CDC，弗若斯特沙利文分析

•RSVisoneofthecomonvirusesthatinfectherespiratorytract.Infectionsoftheuperespiratorytractypicaly

presentwithcold-likesymptoms,whichareusualymildandself-limiting.Insomecases,however,RSVinfectioncan

progrestoalowerespiratorytractinfection,primarilymanifestingasbronchiolitisorpneumonia.

•TheseverityofRSVinfectionisage-dependent,withinfants,thelderly,andadultswithchronicilnesesbeing

consideredhigh-riskpopulations.

RSV-Related Diseases, Transmision Characteristics, and High-

Risk Populations

RSV-Related Diseases

•RSVistransmitedthroughdropletsandthesecretionsof

infectedindividuals.Theviruscansurviveonsurfacesfor

aproximately4to7hours.

•IndividualsinfectedwithRSVareusualycontagiousfor3to

8days.However,someinfantsandpeoplewithweakened

imunesystemscancontinuetospreadthevirusforupto

4weks,evenaftertheirsymptomshavestoped.

RSV Transmision

High-Risk Populations

•Uperespiratorytractinfection:Clinicaly

presentswithsymptomsofuperespiratory

iritation,suchasnasalcongestion,runynose,

cough,andhoarsenes.Congestionandedema

maybeobservedinareasuchasthenasal

mucosa,pharynx,bulbarconjunctiva,and

tympanicmembrane.Feverisalsocomonly

asociated.

•Lowerespiratorytractinfection:Children

infectedwithRSVmaydeveloplower

respiratorytractinfections,primarilypresenting

asbronchiolitisorpneumonia.

•High-riskpopulationsforsevereRSVinfection

include:

✓Prematureinfants

✓Infantsaged6monthsoryounger

✓Childrenunder2yearsoldwithchronic

lungdiseaseorcongenitalheartdisease

✓Childrenwithweakenedimunesystems

✓Childrenwithneuromusculardisorders,

includingthosewhohavedificulty

swalowingorclearingmucusecretions

•High-riskpopulationsforsevereRSVinfection

include：

✓Elderly individuals, especialy those

aged 65 and older

✓Adults with chronic heart or lung

diseases

✓Adults with weakened imune systems

Infants

Elderly individuals & Adults with chronic

ilneses

资料来源：WHO，CDC，弗若斯特沙利文分析

Brand Name (Generic Name)	Technical Route	Manufacturer	FDA approval date*	Age Coverage

Marketed RSV Vacinesin global market

ABRYSVOrecombinantPfizer2023/05

32-36 weks gestational age; 60

years of age and older; 18-59 years of

age who are at increased risk

AREXVYrecombinantGSK2023/05

60 years of age and older; 50-59

years of age who are at increased risk

mRESVIAmRNAModerna2024/0560 years of age and older

Note: The aproval date is the time when the vacine was first aproved, without considering the expansion of the age group of the vacinated population

By end of July 21

, 2025

Source：FDA, Frost & Sulivan

8.3 Unit: Billion USD 6.5 4.9 3.5 2.4 2.5 1.9 1.5 1.6 1.3 1.4 – – – –
2019 2020 2021 2022 2023 2024 2025E 2026E 2027E 2028E 2029E 2030E 2031E 2032E 2033E

Global RSV Vacine Market Size and Forecasted, 2019-2033E

•Sincethe1960s,thedevelopmentofRSVvacineshasbenapriorityfortheWHO.InMay2023,Arexvybecametheworld’sfirst

aprovedRSVvacine,folowedcloselybyPfizer’sAbrysvo,whichalsoreceivedFDAaproval.OnMay31

ofthisyear,mResvia

developedbyModernabecamethethirdRSVvacineaprovedbytheFDA.Asofnow,therearenorelevantvacineproducts

aprovedinChina.

•TheglobalmarketsizeforRSVvacinesisexpectedtoreach1.5bilionUSDin2024.From2024to2033,RSVproductsalesare

expectedtogrowatCAGRof20.6%,withmarketsizereaching8.3bilionUSDin2033.

Global RSV Vacine Market Size and Forecasted, 2019-2033E

Source: Expert interview, Anual Report, Frost & Sulivan analysis

PeriodCAGR

2019-2024-

2024-2033E20.6%

1	Overview of the human vaccine market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

3.1	Overview of the human rabies vaccine market

3.2	Overview of the zoster vaccine market

3.3	Overview of the broad spectrum orthopoxviral vaccine

3.4	Overview of the varicella vaccine

3.4	Overview of the tetanus vaccine

Polymerase
Phosphoprotein

Overview of Rabies

•Rabiesisavacine-preventablezonoticviraldiseasethatocursinover150countriesandregions.Onceclinical

symptomsapear,rabiesisnearly100%fatal.Rabiesvacineisanactiveimunizingagentusedtopreventinfection

causedbytherabiesvirus.Thevacineworksbycausingyourbodytoproduceitsownprotection(antibodies)against

therabiesvirus.

Source: WHO, Frost & Sulivan

Bite

Saliva containing Rabies virus

Rabies virus

GlycoproteinEnvelopeMatrix

protein

cleoprotein

•Therabiesvirusbelongstothe

Mononegaviralesorder,Rhabdoviridae

family,andLysavirusgenus.

•Thevirusparticlesarebulet-shaped,

measuring100-300nminlengthand

aproximately75nmindiameter.

•Theviralgenomeisabout12kbin

lengthandsequentialyencodesfive

structuralproteins:nucleoprotein,

phosphoprotein,matrixprotein,

glycoprotein,andRNA-dependentRNA

polymerase.

sParalytic

Furiousrabiesisprimarilycharacterizedbyconfusion,

phobicspasms,andautonomicdysfunction,suchaspupil

dilationandexcesivesalivation.

Inparalyticrabies,patientsremainconsciousbutexhibit

neurologicalsymptomsimilartoGuilain-Barésyndrome,

includingprogresive,ascending,symetricalparalysis,

flacidlimbweaknes,andvaryingdegresofsensory

impairment.

Symptoms

Transmision routes

Treatment

•Therabiesvirusistransmitedthrough

directcontactwiththesalivaor

brain/nervousystemtisueofaninfected

animal(forexample,throughbrokenskinor

mucousmembranesintheyes,nose,or

mouth).

•Inaditiontobitesandscratches,other

modesoftransmisionarerare,suchas

rabiesaerosolexposureororgan

transplantsfromrabies-infectedonors.

Curently,thereisnoefectivemedicaltreatmentfor

rabies;onceclinicalsymptomsapear,thediseaseis

nearly100%fatal.Treatmentforabiesprimarily

focusesonpost-exposureprophylaxis(PEP)to

preventhevirusfromreachingthecentralnervous

system.

PEPincludes:

•Imediateandthoroughwashingandlocal

treatmentofthebiteorscratchsiteaftersuspected

exposure;

•AdministrationofaWHO-aprovedrabiesvacine

regimen;

•Useofrabiesimuneglobulin(RIG).

Furious

Rabies Risk Levels in Diferent Countries and Regions Worldwide

•TheUKDepartmentofPublicHealthasconductedapost-exposureriskasesmentfordiferentregionsandcountries

worldwidebasedonthepresenceofrabiesinlivestockandwildlife.

•Alregionsareconsideredlow-riskforabiesexposurefolowingcontactwithprimatesandrodents.However,exceptfor

theUKandIreland,alareasworldwideareconsideredhigh-riskforabiesexposurefrombats.

•MostregionsinAsia,Africa,SouthAmerica,andCentralAmericareclasifiedashigh-riskforabiesexposurefrom

terestrialanimals,includingChina.TheChineseCDCrecomendsimediatepost-exposureprophylaxis,including

rabiesvacination,afteranyinjuryfromhigh-riskanimals(dogs,cats,strayorwildmamals,andbats).Curently,there

ishighdemandforabiesvacinesinChina.

High-Risk Regions: Rabies ocurs in

both wildlife and companion animals.

Low-Risk Regions: Rabies ocurs in

wildlife but not in companion animals.

No-Risk Regions: No indigenous

rabies in terestrial animals.

Source: Public Health England, Frost & Sulivan

Risk Levels for Rabies Exposure

Folowing Contact with Terestrial

Animals

Exposure Category	Contact Mode	Exposure Level	Post-Exposure Immunoprophylaxis
I	Meets any of the following: • Touching or feeding animals • Intact skin exposed to animal saliva • Intact skin contact with excreta or secretions from healthy animals or confirmed rabies- free animals	None	If the contact method is reliable, no treatment is needed.
II	Meets any of the following: • Minor scratches or abrasions on bare skin without bleeding • Licks on broken skin	Mild	• Wound treatment • Rabies vaccination
III	Meets any of the following: • Single or multiple transdermal bites or scratches • Broken skin exposed to animal saliva • Mucosal contact with saliva (e.g., licks on open wounds) • Exposure to bats	Severe	• Wound treatment • Administration of rabies immunoglobulin (RIG) (anti-rabies serum or rabies immune globulin) • Rabies vaccination

Rabies Vacination Scenarios

Pre-Exposure

Prophylaxis

Post-Exposure

Prophylaxis

VacinationSchedules

•5-DoseSchedule:Administeronedoseondays0,3,7,14,and28,totaling5doses.

•Simplified4-DoseSchedule:Reducesthefinaldosefromthe5-doseschedule,with

dosesadministeredondays0,3,7,and14-28,totaling4doses.

•”2-1-1″Schedule:Administertwodosesonday0(oneineachdeltoidmuscleofthe

uperarms),folowedbyonedoseonday7andanotheronday21,totaling4doses.

(Thischeduleisonlyaplicableforabiesvacinesaprovedforthe”2-1-1″

scheduleinChina.)

Source: China CDC, Frost & Sulivan

•PrimaryImunization

Itisrecomendedthatalindividualswho

arecontinuouslyorfrequentlyexposedto

environmentswithariskofrabiesreceive

pre-exposureprophylacticrabiesvacination.

VacinationSchedule

Thredosesareadministeredonday0,day

7,anday21(orday28).

•BosterImunization

Regularbosterimunizationis

recomendedonlyforindividualswith

continuous,frequent,orhigh-riskexposure

torabiesvirusduetocupationalreasons

(e.g.,laboratorypersonelworkingwith

rabiesvirusandveterinarians).

ImunizationSchedule

•Laboratorypersonelexposedtorabies

virushouldmonitortheirserum

neutralizingantibodylevelsevery6

months.

•Veterinariansandpersonelinanimal

epidemicontroldepartmentshould

monitortheirserumneutralizing

antibodylevelsevery2years.

•Abosterdoseshouldbeadministered

iftheserumneutralizingantibodylevel

is<0.5IU/ml.

Source: WHO, Frost & Sulivan

•Acording to the Rabies vacines: WHO position paper –April 2018, Rabies is a viral zonotic disease responsible for an estimated 59

thousand human deaths in 2015. Most cases ocur in Africa and Asia, with aproximately 40% of cases in children aged <15 years, which

indicates the huge demand in developing countries.

•Acording to the WHO Zero Human Rabies Deaths from dog-transmited rabies by 2030 (Zero by 30), each country pays efort to control this

disease with diferent methods.

•Human rabies vacine is esential for prevention of rabies, especialy after exposure to rabies, in which case the mortality rate is nearly 100%

without post-exposure prophylaxis.

Comparison of Rabies solutions in Developed and Developing

Countries

Developing

countries

Developed

countries

•Animal rabies vacines for pets

is the majority of rabies vacine

used in countries with low risk of

human rabies.

•Human rabies vacine for PEP

is the majority of rabies vacine

used in developing countries

with high incidence and death

tol of rabies.

Type of rabies vacine

•In some developed countries

with established animal disease

control system, such as the US

and Japan, rabies is a rare

disease and only several new

cases are reported each year.

•For these countries, the main

method to control and prevent

rabies is vacination for pets.

•Over 95% of human deaths with

rabies is ocuring in

developing countries inAsia and

Africa regions.

•For these countries with high

bite incidence and morality,

imediate PEP is the most

efective way to control the

death tol of rabies.

Curent situation

•With the low incidence of rabies

in developed countries,

prevention vacination for

animals wil kep its role as the

main method to control rabies.

Trend

•As the incidence of rabies in

these countries is predicted to

kep a high level in the next few

years, the demand of human

rabies vacine wil stil kep a

high level.

•With the growing awarenes of

prevention of rabies, animal

vacination wil also raise the

atention. For instance, mas

dog vacination was initiated in

Bangladesh in 2011 with the

help from WHO.

Typical countries

•India

•Egypt

•Bangladesh

•Thailand

•Philipines

•U.S.

•Japan

•Australia

•England

Number of New Cases and Deaths of Rabies in China，2019-2024

•AcordingtotheStatisticalReportonChina’sHealthCareDevelopment（卫生健康事业发展统计公报）,therewere170

newcasesofrabiesand143deathsfromrabiesinChinain2024.

New Cases of Rabies in China，2019-2024Deaths of rabies in China，2019-2024

Source：Statistical Report on China’s Health Care Development, Frost & Sulivan

	Introduction	Immunogenicity	Safety	Cost & Yield	Challenges
Primary Cell
	• PCEC	• Qualified immunogenicity	• For PCEC, egg ingredients may cause allergic reactions	• Relatively high cost • Rely on the supply of high standard eggs	• Risk of insufficient supply • Time-consuming
	• PHKC	• Qualified immunogenicity	• –	• Low cost • Adherent culture needed, difficulties in scale up	• Easy to be contaminated • Cell preservation is tedious
	• Isolated from kidney epithelial cells extracted from an African green monkey	• Qualified immunogenicity	• Presence of residual host cell DNA	• Low cost	Potential tumorigenicity of the DNA of high- passage Vero cells
Vero Cell
	• Usually derived from cell lines established from normal human fetal tissue. • Mainly includes MCR-5, 2BS, EI- 38 cell line.	• Qualified immunogenicity • Neutralizing antibodies produce faster and better antibody responses	• No residual host cell proteins and foreign DNA in vaccines, can significantly reduce adverse reactions	• High cost • Difficulties in scale up	• Strict requirements for environmental control, medium formulation, and cultivation techniques
Human Diploid Cell

•Theproductionofhigh-qualityrabiesvacineshasbenmadefeasiblethroughmoderncelcultivationtechniquesusing

diploidcelstrainsforvacineproduction.Humandiploidcelvacine(HDCV)isavacineculturedandmanufactured

usinghealthyhumanembryoniclungfibroblastsasamatrix.Itisoftenusedasareferencevacinebecauseithasno

potentialtumor-causingDNAresiduesoriskoforeignproteinalergens,andistheoreticalysafer.

•TheWHOrecomendshumandiploidcelsasoneofthesafestcelculturesubstratesfortheproductionofviral

vacines.Althoughthereareonlytwohumandiploidcelrabiesvacinescurentlyavailableonthemarket.Inthenext2-

3years,theproductionofhumandiploidrabiesvacinesisexpectedtoincrease,andhumandiploidrabiesvacinesare

expectedtobecomeoneofthemainparticipantsintherabiesvacinemarket.

Traditional

Cel Line

Inovative

Cel Line

Analysis of Diferent Cel Lines for Rabies Vacine

Source: Frost & Sulivan

58.8

78.6

88.0

83.3

72.3

77.8

•Duetothenegativeimpactofthe“ChangchunChangshengVacineEvent”(“长春长生疫苗事件”),lotreleaseofrabiesvacines

hasexperiencedadownwardtrendin2018and2019.Until2020,lotreleaseofrabiesvacinereturnedtoriginalevel.

•Thelotreleaseofrabiesvacinexperiencedafluctuationfrom58.8milionin2019to77.8milionin2024,withaCAGRof5.8%.

Lot Release of Rabies Vacinein China , 2019-2024

PeriodCAGR

2019-20245.8%

Unit: Milion

Source: Expert interview, NIFDC, Frost & Sulivan analysis

Lot Release of Rabies Vacine in China, 2019-2024

0.1 7.4
5.4

0.1 7.5
5.0

0.1 7.5
4.5

0.1 7.5
4.1

0.2 7.5
3.7

0.2 7.4
3.4

7.3
2.6

0.1 7.2
2.4

7.3
2.7

7.3
3.0

0.1 6.5
2.3

6.5
1.1

0.05 4.9
1.1

0.1 3.1
0.6

0.6

2.3

7.2

0.1

0.05

1.8

0.2

0.1

0.2

0.1

3.8

6.0

9.4

10.1

8.9

9.5

9.8

10.1

10.5

10.9

11.4

11.8

12.2

12.6

13.0

2019202020212022202320242025E2026E2027E2028E2029E2030E2031E2032E2033E

Human diploid celVero celOthers

China Rabies Vacine Market Production Value, Separated by Cel

Lines, 2019-2033E

China Rabies Vacine Market Production Value, 2019-2033E

Unit: Bilion RMB

Source: Expert interview, NIFDC, Frost & Sulivan analysis

Period

CAGR

Human diploid celVero celOthersTotal

2019-202429.1%18.5%2.2%20.3%

2024-2033E10.2%0.4%3.2%3.5%

•The rabies vacine market in China, in terms of production value, increased from RMB3.8 bilion in 2019 to RMB9.5 bilion in 2024,

at a CAGR of 20.3%. The total number of lot release increased from 58.8 milion in 2019 to 77.8 milion in 2023. Driven by

increase in vacination rates and the introduction of high-value rabies vacines, the rabies vacine market in China is estimated to

further increase to RMB13.0 bilion in 2033, at a CAGR of 3.5% from 2024 to 2033.

Cell Line	Brand Name (Generic Name)	Company	NMPA approval date	Immunization Schedule3	End-User Price1	Market Share2 (2024)

(Generic Name)aproval dateSchedulePrice(2024)

Human Rabies

Vacine

(Vero Cel)

武生旺宁

Wuhan institute of biological products

（武汉生物制品研究所）

2004/01Esen 5 doses/-

成大速达

ChengdaBiotechnology

（成大生物）

2004/01

Zagreb 4 doses & Esen 5

doses

89.5-

–

HK Biotech

（惠康生物）

2006/11Esen 5 doses80-

–

Fosun Apexvac

（复星雅立峰）

2016/09Esen 5 doses742.5%

Human Rabies

Vacine, lyophilized

(Vero Cel)

–

YishengBiopharma

（依生物）

2003/04Esen 5 doses9518.8%

–

ChengdaBiotechnology

（成大生物）

2004/01

Zagreb 4 doses & Esen 5

doses

9832.3%

武生欣宁

Wuhan institute of biological products

（武汉生物制品研究所）

2005/01Esen 5 doses/-

–

AIM

（艾美疫苗）

2007/09Esen 5 doses996.1%

–

PRCMISE Biological

（诺诚生物）

2008/01Esen 5 doses/-

–

ZhuoyiBiological

（卓谊生物）

2016/11Esen 5 doses118.56.7%

–

Changchun institute of biological

products

（长春生物制品研究所）

2021/04

Zagreb 4 doses & Esen 5

doses

9911.7%

–

YiduBiotechnology

（亦度生物）

2021/07

Zagreb 4 doses & Esen 5

doses

9110.0%

–

Hualan Biological Bacterin

（华兰生物）

2023/04

Zagreb 4 doses & Esen 5

doses

1291.2%

–

CuroVax

（康润生物）

2023/09

Zagreb 4 doses & Esen 5

doses

158-

–

Fosun Apexvac

（复星雅立峰）

2024/03Esen 5 doses113-

Marketed Human Rabies Vacinesin China(1)

Source：NMPA, Frost & Sulivan

Cell Line	Brand Name (Generic Name)	Company	NMPA approval date	Immunization Schedule3	End-User Price1	Market Share2 (2024)

Marketed Human Rabies Vacinesin China(2)

(Generic Name)aproval dateSchedulePrice(2024)

Human Rabies Vacine,

lyophilized

(Human Diploid Cel)

–

KanghuaBiological Products

（康华生物）

2012/01Esen 5 doses3155.0%

–

MINHAI

（民海生物）

2023/09

Zagreb 4 doses &

Esen 5 doses

2984.3%

Human Rabies Vacine

(Hamster Kidney Cel)

–

Yataibiopharmaceuticals

（亚泰生物）

1999/01Esen 5 doses/-

–

CGE Healthcare

（远大生物）

2000/01Esen 5 doses791.4%

–

Lanzhou institute of biological

products

（兰州生物制品研究所）

2000/01Esen 5 doses/-

–

ZhongkeBiotic

（中科生物/博晖生物）

2000/02Esen 5 doses95-

–

AIM

（艾美疫苗）

2006/01Esen 5 doses/-

Human Rabies Vacine,

lyophilized

(Hamster Kidney Cel)

–

Lanzhou institute of biological

products

（兰州生物制品研究所）

2005/01Esen 5 doses/-

Source：NMPA, Frost & Sulivan

Note:

1.The end-user price is determined by the median of wining bid prices in provinces with publicly disclosed data in 2024;

2. The market share was calculated by Production volume;

3. Post exposure vacination program, in adition, al aproved products can be used for the pre exposure prophylaxis 3-dose imunization program

4. Certain human rabies vacines are aplicable to two imunization schedules, as they have undergone clinical validation andare proven to achieve the desired

efects under each schedule. The decision of which schedule to adopt is primarily determined by the vacine itself, and its administration should folow the

instructions provided in the medication guide;

5. Including the lyophilized and non-lyophilized type of the company’s human rabies vacines;

6. By end of July 21

, 2025

Cell Line	Company	Clinical Stage	FPD*	Immunization Schedule

Competitive Landscape of Rabies Vacines in China (1)

Source: CDE, Frost & Sulivan

Vero cel

NuochengBiological Products

（诺辰生物）

NDA2024/07/26Zagreb 4 doses & Esen 5 doses

Sinovac

（科兴）

NDA2025/1/251-1-1-1 & Esen 5 doses

Ronsen

（荣盛生物）

NDA2025/03/13Esen 5 doses

AIM

（艾美疫苗）

NDA2025/04/08Esen 5 doses

GDK biotechnology

（金迪克生物）

I (completed)2017/12/20Esen 5 doses

MaokangyuanBiotechnology

（茂康源生物）

I2019/12/25Esen 5 doses

ZFSW

（智飞生物）

I2020/12/10Zagreb 4 doses & Esen 5 doses

ChengdaBiotechnology

（成大生物）

I (completed)2021/07/281-1-1-1

I2025/02/24Esen 5 doses

RBSPH

（银河阳光生物制品）

I2022/11/041-1-1-1 & Esen 5 doses

YishengBiopharmaceutical

（依生物）

I2024/11/121-1-1-1 & Zagreb 4 dose

YiduBiotechnology

（亦度生物）

I2025/06/171-1-1-1

YataiBiological Pharmaceutical

（亚泰生物药业）

I (completed)2021/02/23Esen 5 doses

Cell Line	Company	Clinical Stage	FPD*	Immunization Schedule

Competitive Landscape of Rabies Vacines in China (2)

*Note: The dates for products in NDA stage are the dates handled by CDE

By end of July 21

, 2025

Source: CDE, Frost & Sulivan

Chicken Embryo Cel

King-cel Biotechnology

（青赛生物）

NDA2024/10/18Zagreb 4 doses & Esen 5 doses

Qingfeng/C-FUSION

Biotechnology

（青峰药业/赛尔富森生物科技）

I2022/01/18Zagreb 4 doses & Esen 5 doses

Human Diploid Cel

ChengdaBiotechnology

（成大生物）

NDA2024/08/31

Zagreb 4 doses & Esen 5 doses & 1-1-

1-1

ZFSW

（智飞生物）

NDA2024/10/16Zagreb 4 doses & Esen 5 doses

Chengdu institute of biological

products

（成都生物制品研究所）

I2017/05/10Zagreb 4 doses & Esen 5 doses

ProkangBiotechnology

（普康生物）

I2024/07/18Zagreb 4 doses & Esen 5 doses

AIM

（艾美疫苗）

I2025/06/11

Zagreb 4 doses & Esen 5 doses & 1-1-

1-1

I2025/05/19Zagreb 4 doses & Esen 5 doses

Ab&bBiotechnology

（中慧生物）

I (completed)2023/11/20Zagreb 4 doses & Esen 5 doses

Cell Line	Brand Name (Generic Name)	Company	NMPA approval date	Immunization Schedule*

Marketed Human Rabies Vacinesin Global Market

Human Diploid

Cel

ImovaxSanofiNAEsen 5 doses

Primary chicken

embryo cel

RabAvert/RabipurBavarian Nordic1997Esen 5 doses

*Note: Post exposure vacination program, in adition, al aproved products can be used for the pre exposure prophylaxis 3-doseimunization program

By end of July 21

, 2025

Source：FDA, Frost & Sulivan

Cell Line/Technical Route	Company	Clinical Stage	FPD	Immunization Schedule	Locations

Competitive Landscape of Rabies Vacines in Global Market

By end of July 21

, 2025

Source: ClinicalTrials.gov, Frost & Sulivan

Route

Vero cel

Sanofi I (completed)2017/05/102-2-2-2Thailand

YishengBiopharma

I2022/12/292-2-1 & Esen 5 dosesPakistan, Philipines

I (completed)2016/11/061-1-1-1 & 2-2-1Singapore

Sinovac

（科兴）

I2025/07/09Esen 5 dosesPakistan

I2025/07/08PrEP1-1-1Pakistan

mRNACureVacI (completed)2018/10/191-1-1 & 1/2-1/2Belgium, Germany

saRNAGSKI (completed)2019/08/201-1U.S.

Growth Drivers and Future Trends of the Chinese rabies vacine

market

•ThehumanrabiesvacinedevelopedfromhumandiploidcelistheWHO’sgoldstandard

forabiesvacines,oferinghighersafetyandstrongerimuneresponses.Whilethe

curentpriceofsuchvacines,whichismuchigherthanotherhumanrabiesvacines,

impactsvacinationrates,technologicaladvancementsmayreduceproductioncosts,

improvingafordability.Witheconomicgrowth,themarketshareofhumandiploidcelrabies

vacinesisanticipatedtorise.

Growth in Human

Diploid Cel Rabies

Vacine Market

•ThenumberofpetownersinChinaisrising,withasignificantincreaseinpetdogs.

AcordingtoChineseCDC,In2024,thenumberofurbandogsandcatsinChinawilbe

124.11milion,ofwhich52.58milionarepetdogs.However,acordingtoWHO’sWorld

HealthStatisticsreports,over95.0%ofhumanrabiescasesworldwidearecausedbydog-

relatedinjuries.Unlikedevelopednations,Chinahasnotyetefectivelyimplemented

widespreadanimalvacinationprograms,leadingtohigherdemandforhumanrabies

vacines.

Increase in pet

ownership

•Higherpercapitadisposableincomenablesmorepeopletoafordself-fundedvacineslike

humanrabiesvacines.

•In2015,WHOproposedaglobalstrategicplantoeliminatehumanrabiescausedbydogs

worldwideby2030atheGlobalRabiesConferenceheldinGeneva,Switzerland.Inrecent

years,Chinahasalsoreleasedaseriesofguidelines,suchasthe“ExpertConsensuson

RabiesExposurePreventionandTreatment(《狂犬病暴露预防处置专家共识》）“in2019,

“GuidelinesforRabiesExposurePreventionandTreatment(2023Edition)（《狂犬病暴露

预防处置工作规范（2023年版）》）“,whichrecomendedthatindividualswhoare

continuouslyandfrequentlyexposedtorabiesvirushazardousenvironmentshouldreceive

prexposureprophylacticrabiesvacination,andforpostexposureprophylactictreatment,

rabiesvacinationshouldbeadministeredasearlyasposible.Variousprovincesandcities

inChinahavealsosetup24-hourdoginjuryclinicsandmadepublicthelistohelpimprove

thevacinationrateafterexposure.

Increased

afordability and

vacination

awarenes

Source: Frost & Sulivan

Growth Drivers and Future Trends of the Chinese rabies vacine

market

•ThehumanrabiesvacinedevelopedfromhumandiploidcelistheWHO’sgoldstandard

forabiesvacines,oferinghighersafetyandstrongerimuneresponses.Whilethe

curentpriceofsuchvacines,whichismuchigherthanotherhumanrabiesvacines,

impactsvacinationrates,technologicaladvancementsmayreduceproductioncosts,

improvingafordability.Witheconomicgrowth,themarketshareofhumandiploidcelrabies

vacinesisanticipatedtorise.

Growth in Human

Diploid Cel Rabies

Vacine Market

•Inthearlystagesofthedevelopmentofrabiesvacines,naturalanimalfluidsuplements

suchasanimalserum(suchasnewbornbovineserum,premiumfetalbovineserum,etc.)

wereadedtoculturedcelstomaintaincelgrowth.However,thecompositionofserum

culturemediaiscomplex,andvirusesandmycoplasmapresentinanimalserum,aswelas

prionsrelatedtobovinespongiformencephalopathy,poseahighriskofcontamination.In

adition,China‘sbovineserumishighlydependentonimports,whichlimitsitsuply.

Serumfreculturecansolvetheabovepainpoints,withtheadvantagesofstable

components,lowpolution,andhighsafety.TheNationalDevelopmentandReform

Comision’s“GuidingCatalogueforIndustrialStructureAdjustment(2019Edition)（《产

业结构调整指导目录（2019年本）》）”encouragesthedevelopmentandaplicationof

“serum-freandproteinfreculturemediumcultivation,fermentation,andpurification

technologiesformajordiseasepreventionandcontrolvacines”.However,serum-fre

culturetechnologyhashighbariers,andwiththecontinuousupgradingofrabiesvacine

celmatrixculturetechnology,serum-freculturetechnologyisgradualybeingapliedand

wilbecomeafuturetrend.Therearealreadyrelevantpracticesoflowserumandserum-

frecultivationofdiploidcelsinhumans,whichwilpromotethedevelopmentoftherabies

vacinemarket

Upgrading of

serum-fre culture

and other

proceses

promotes further

development of

rabies vacines

Source: Frost & Sulivan

1	Overview of the human vaccine market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

3.1	Overview of the human rabies vaccine market

3.2	Overview of the zoster vaccine market

3.3	Overview of the broad spectrum orthopoxviral vaccine

3.4	Overview of the varicella vaccine

3.4	Overview of the tetanus vaccine

• Shingles, also known as HZ, is a disease caused by reactivation of the varicella-zoster virus (VZV) from dorsal sensory or cranial nerve ganglia. This reactivation occurs when immunity to VZV declines because of aging or immunosuppression. Herpes zoster can occur at any age but most commonly affects the elderly population. Symptoms of shingles usually include a general feeling of malaise, pyrexia, chills, myalgia, headache, pruritus, numbness and rash. VZV can be spread from a person with active shingles to another person who has never had varicella or received vaccines. Following the resolution of varicella, the virus can remain dormant in the dorsal sensory and cranial ganglion for decades.

Symptoms

Complications
• The most common complication of shingles is long-term nerve pain called postherpetic neuralgia (PHN). PHN occurs in the areas where the shingles rash was, even after the rash clears up. It can last for months or years after the rash goes away. The pain from PHN can be so severe and debilitating that it interferes with daily life. • Shingles may lead to serious complications involving the eye, including blindness. • Very rarely, it can also lead to • pneumonia, • hearing problems, • brain inflammation (encephalitis), or • death.
Risk Factors
• The risk of getting shingles and having serious complications increases with age. • People who have medical conditions or take medications that keep their immune systems from working properly have a higher risk of getting shingles.

Overview of Shingles

•Shingles is a painful rash that develops on one

side of the face or body. The rash consists of

blisters that typicaly scab over in 7 to 10 days

and fuly clears up within 2 to 4 weks.

•Before the rash apears, people often have pain, itching, or

tingling in the area where it wil develop. This may hapen

several days before the rash apears.

•Most comonly, the rash ocurs in a single stripe around

either the left or the right side of the body. In other cases,

the rash ocurs on one side of the face.

•Shingles on the face can afect the eyeand cause vision los.

In rare cases (usualy in people with weakened imune

systems), the rash may be more widespread on the body and

lok similar to a chickenpox rash.

•Other symptoms of shingles can include

•Fever

•Headache

•Chils

•Upset stomach

Source: Literature review, Frost & Sulivan analysis

VZV tra
VZV tra

CD4 T cell
VZV
NK cell

Overview of Varicela-Zoster Virus

VZV Reactivation Leadsto HZ.

•Active herpes zoster

lesions are infectious,

through direct contact

with vesicular fluid, until

they dry and crust over.

•People with active herpes

zoster lesions can spread

VZV infection and cause

varicela in people who

have never had varicela or

received varicela vacine.

•Once varicela resolves,

these people would be at

risk of herpes zoster.

•People with active herpes

zoster lesions should

cover their lesions and

avoid contact with

susceptible people in

their household and in

ocupational setings until

their lesions are dry and

crusted.

Transmision

•Shingles is caused by varicela zoster virus (VZV), the same virus that causes

chickenpox (varicela).

•Primary infection with VZV causes varicela.

•After a person recovers from chickenpox, the virus stays dormant (inactive) in

the dorsal rot ganglia.

•The virus can reactivate later in a person’s life and cause a painful,

maculopapular rash caled herpes zoster.

VZV reactivates

in the dorsal

rot ganglia

VZV travels

down nerve

terminals

Interferon

Dendritic cel

Macrophage

CXCL10

CD8 T cel

NK cel

Keratinocyte

VZV-loaded

blister

Polykaryocyte

Spinal cord

Epidermis

Rash

Source: Literature review, Frost & Sulivan analysis

• Humans are the only host of varicella-zoster virus. The virus enters the blood through the respiratory mucosa to form viremia. Varicella or recessive infection occurs. Later, the virus can be latent in the spinal dorsal root ganglia or cranial nerve sensory ganglia for a long time. Shingles affects nearly 3 million Chinese adults each year and most of them occur in adults over 50. According to the epidemiological survey in Guangdong Province, the prevalence rate of women is significantly higher than that of men.

Transmission

Overview of Zoster (Herpes Zoster)Vacine

•Saliva spread

•Shingles is transmited through the liquid

of leakingherpes.

•Shingles can be spread through wounds

•Blod-borne infection

•Placental infection

Body Fluid

Transmision

Wounds

Transmision

Blod

Transmision

Placental

Transmision

•SHINGRIX is a zoster vacine

developed by GlaxoSmithKline. This is

the only aproved zoster vacine in

China.

•The vacine is a kind of recombinant

zoster vacine which is capable of

providing 90% protection among

people over 50 years old acording to

clinical data.

•Zostavax is azoster vacine developed

by Merck. The vacine wasn’t aproved

in China mainland.

•As a earlier developed vacine,

Zostavax aplied atenuated vacine

technique which have several draw

backs compared with recombinant

zoster vacine .

Draw Backs

•The price of Shingrix in China is 1560 CNY each dose and it usualy takes 2 doses for each

person, which reveals the lack of price advantage.

•The adverse reactions includes pain, rednes, sweling, myalgia, fatigue, headache, chils,

fever, and gastrointestinal symptoms.

Source: Literature review, Frost & Sulivan analysis

2024-2033E 13.2% 23.8 20.7 Unit: Billion RMB 17.8 15.1 12.5 10.2 8.6 7.8 7.6 7.0 2.6 2.7 0.9 0.8
2020 2021 2022 2023 2024 2025E 2026E 2027E 2028E 2029E 2030E 2031E 2032E 2033E

China Zoster Vacine Market Production Value, 2020-2033E

•TheherpeszostervacinemarketinChinareachedRMB2.6bilionintermsofproductionvaluein2020afterthefirstherpeszoster

vacineobtainedaprovalfromtheNMPAin2019.Drivenbygrowingawarenesofherpeszosterandtheincreasingnumberof

availableherpeszostervacineproducts,theherpeszostervacinemarketisestimatedtoincreasefromRMB7.8bilionin2024to

RMB23.8bilionin2033,ataCAGRof13.2%.

China Zoster Vacine Market Production Value, 2020-2033E

PeriodCAGR

2020-202431.2%

Source: Expert interview, NIFDC, Frost & Sulivan analysis

8.7 7.8 Unit: Billion USD 7.0 6.2 5.6 5.1 4.8 4.9 4.7 4.4 4.4 3.7 2.6 2.4 2.4
2019 2020 2021 2022 2023 2024 2025E 2026E 2027E 2028E 2029E 2030E 2031E 2032E 2033E

Global Zoster Vacine Market Size and Forecasted, 2019-2033E

•TheglobalherpeszostervacinemarketincreasedfromUS$2.4bilionin2019toUS$4.4bilionin2024,ataCAGRof12.8%,and

isestimatedtoreachUS$8.7bilionin2033,ataCAGRof7.8%from2024to2033.

Global Zoster Vacine Market Size and Forecasted, 2019-2032E

Source: Expert interview, Anual Report, Frost & Sulivan analysis

PeriodCAGR

2019-202412.8%

2024-2033E7.8%

Brand Name (Generic Name)	Technical Route	Company	FDA approval date*	Age Coverage

Marketed Zoster Vacinesin global market

Zostavaxlive atenuatedMerck2006/0550 years of age and older

SHINGRIXrecombinantGSK2017/10

50 years and older/18 years and

older who are or wil be at

increased risk

Note: The aproval date is the time when the vacine was first aproved, without considering the expansion of the age group of the vacinated population

By end of July 21

, 2025

Source：FDA, Frost & Sulivan

Brand Name (Generic Name)	Technical Route	Company	NMPA approval date*	Age Coverage

Marketed Zoster Vacinesin China

SHINGRIXrecombinantGSK2019/0550 years of age and older

感维live atenuated

BCHT

（百克生物）

2023/0140 years of age and older

Note: The aproval date is the time when the vacine was first aproved, without considering the expansion of the age group of the vacinated population

By end of July 21

, 2025

Source：NMPA, Frost & Sulivan

Technical Route	Company	Clinical Stage	FPD*	Age Coverage

Competitive Landscape of Zoster Vacines in China

*Note:The dates for products in NDA stage are the dates handled by CDE

By end of July 21

, 2025

Source: CDE, Frost & Sulivan

recombinant

Recbio

（瑞科生物）

I2024/10/940 years of age and older

recombinant

Lvzhubiotech

（绿竹生物）

NDA2025/2/9

*The age for submiting NDA for this

product has not ben disclosed

I2023/9/2540 years of age and older

I2024/11/450 years of age and older

I (completed)2022/4/1950-70 years of age

recombinant

MaxVax

（迈科康生物）

I2024/6/340 years of age and older

I2023/5/830 years of age and older

I2022/10/2118 years of age and older

recombinant

Varnotech

（华诺泰生物）

I2024/10/2940 years of age and older

recombinant

Ab&bBiotechnology

（中慧生物）

I/I2025/2/1940 years of age and older

recombinant

SinoCelTech

（神州细胞工程）

I/I2025/1/2440 years of age and older

recombinant

Lvyepharma

（绿叶制药）

I2025/3/540 years of age and older

recombinant

CGE Healthcare

（远大赛威信）

I2024/12/1040 years of age and older

recombinant

Shanghai institute of biological

products

（上海生物制品研究所）

I2025/4/2540 years of age and older

recombinant

GeneVax

（吉诺卫）

I2025/6/1040 years of age and older

live atenuated

Changsheng biotechnology

（长生物）

I2017/10/740 years of age and older

live atenuated

Shanghai institute of biological

products

（上海生物制品研究所）

I/I (completed)2018/12/1940 years of age and older

Technical Route	Company	Clinical Stage	FPD*	Age Coverage

Competitive Landscape of Zoster Vacines in China

*Note:The dates for products in NDA stage are the dates handled by CDE

By end of July 21

, 2025

Source: CDE, Frost & Sulivan

recombinant

Recbio

（瑞科生物）

I2024/10/940 years of age and older

recombinant

Lvzhubiotech

（绿竹生物）

NDA2025/2/9

*The age for submiting NDA for this

product has not ben disclosed

I2023/9/2540 years of age and older

I2024/11/450 years of age and older

I (completed)2022/4/1950-70 years of age

recombinant

MaxVax

（迈科康生物）

I2024/6/340 years of age and older

I2023/5/830 years of age and older

I2022/10/2118 years of age and older

recombinant

Varnotech

（华诺泰生物）

I2024/10/2940 years of age and older

recombinant

Ab&bBiotechnology

（中慧生物）

I/I2025/2/1940 years of age and older

recombinant

SinoCelTech

（神州细胞工程）

I/I2025/1/2440 years of age and older

recombinant

Lvyepharma

（绿叶制药）

I2025/3/540 years of age and older

recombinant

CGE Healthcare

（远大赛威信）

I2025/7/1140 years of age and older

recombinant

Shanghai institute of biological

products

（上海生物制品研究所）

I2025/4/2540 years of age and older

recombinant

GeneVax

（吉诺卫）

I2025/6/1040 years of age and older

live atenuated

Changsheng biotechnology

（长生物）

I2017/10/740 years of age and older

live atenuated

Shanghai institute of biological

products

（上海生物制品研究所）

I/I (completed)2018/12/1940 years of age and older

Technical Route	Company	Clinical Stage	FPD*	Age Coverage

Competitive Landscape of Zoster Vacines in China

*Note:The dates for products in NDA stage are the dates handled by CDE

By end of July 21

, 2025

Source: CDE, Frost & Sulivan

mRNA

CSPC

（石药集团）

I2025/4/2940 years of age and older

mRNA

ABOGEN

（艾博生物）

I2025/5/1440 years of age and older

mRNA

RHEGEN

（瑞吉生物）

I2025/5/1640 years of age and older

Growth Drivers of zoster vacine Market

•ThelifetimeriskofHerpesZoster(HZ)inthegeneralpopulationrangesfrom20–30%butherisk

increasesdramaticalyafter50yearsofagewithalifetimeriskofHZreaching50%atage85years.

Withtheagingoftheglobalsociety,thenumberofpeopleover50yearsoldisincreasing,indicatinga

growingamountofpeoplethatarepronetoshingles.Peoplewitherpeszosterarelikelytodevelop

postherpeticneuralgia(PHN),whichisthemostcomonandaseverecomplicationofherpeszoster.

PHNcanlastforweks,monthsorevenforyears,whichcandramaticalyafectingthelifequalityofthe

patient.Furthermore,aperson’sriskofhavingPHNafterherpeszosterincreaseswithage,indicatinga

considerablediseaseburdenfortheold.Therefore,efectivevacineofHZareofgreatmarketpotential.

Aging Society

•Acording to studies, Herpes Zoster (HZ)persists for life in the host after a primary infection (varicela or

chickenpox). It is estimated that up to one third of infected individuals wil clinicaly reactivate VZV in

their lifetimes, usualy in their elderly years when imunity is naturaly senescing, or when imunity is

supresed by disease or iatrogenic cause. Each year, more than 1.5 milion people in China are

aflicted by HZ and its most comon complication the persistence of neuropathic pain (post-herpetic

neuralgia, [PHN]), with a total cost of over 1 bilion RMB acros China. Such huge amount of potential

reactivation patient sugest a huge market of HZ vacine.

High Reactivation

Rate

•Zostavax,thefirstzostervacine,wasaliveatenuatedvacineaprovedbytheFDAin2006.Although

Zostavax’seficacydeclinesignificantlywithinsixtoeightyearsaftervacination,themarkethas

evolvedwiththeintroductionofShingrixin2017.Shingrix,arecombinantproteinvacine,ofers

significantlybeterprotectionasproveninclinicaltrials.Thistechnicaladvancementresultedin

Shingrix’srevenuesreachingUS$4.3bilionin2023,whenFDAdiscontinuedlotreleaseofZostavaxin

thesameyear,underscoringanexpandedmarketsharefornewvacines.

Technical Upgrade

Source: Frost & Sulivan analysis

Future Trends of zoster vacine Market

Source: Frost & Sulivan analysis

•Advances in biotechnology and production proces are leading to development of zoster

vacines with improved durability and stronger imunogenic responses. These developments

are suitable not only for healthy individuals but also for the elderly and imunocompromised

population. Inovations such as the mRNA zoster vacine, which are curently being tested in

rhesus monkeys, show promising extended imune responses with aceptable side efects.

Safe and Efective

•Improvedproceses and technology could reduce the cost of producing zoster vacines, thus

lowering their price and driving more people to get vacinated. In adition, the increased safety

and protective eficacy of the herpes zoster vacine can expand the aplicable population of the

vacine. These two factors would increase the penetration of the zoster vacine market.

High Penetration

1	Overview of the human vaccine market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

3.1	Overview of the human rabies vaccine market

3.2	Overview of the zoster vaccine market

3.3	Overview of the broad spectrum orthopoxviral vaccine

3.4	Overview of the varicella vaccine

3.4	Overview of the tetanus vaccine

Virus	Infections in	Spectrum of hosts	Natural host

Overview of Orthopoxvirus

•ThegenusOrthopoxviruswithinthePoxviridaefamilyincludeseveralspecies,suchasthevariolavirus(VARV),which

causesmalpoxandexclusivelyinfectshumans;zonoticspecieslikemonkeypoxvirus(MPXV),cowpoxvirus(CPXV),

vaciniavirus(VACV),andcamelpoxvirus(CMLV);alongwithotherelatedviruses.Theseorthopoxviruseshare

imunologicalcros-reactivityandcros-protection,meaninginfectionwithonevirusinthisgenusprovidesimunity

againstotherswithinthesamegenus.

Orthopoxvirusvirus structure

•StructureandSize:Orthopoxviruses(OPV)are

enveloped,brick-shapedvirusesmeasuring

aproximately350×270nm.

•Genome:Theyposesadouble-strandedDNA

genomeofabout200kb,withcovalentlylinkedends.

•AntigenicRelationship:OPVspecieshareclose

antigenicrelationships.

•GenomicHomology:OPVexhibitsignificantgenome-

levelhomologyacrospecies.

Variola (VARV)humanbroadunknown

Vacinia (VACV)

human, bufalo, catle, elephant,

pig, rabit, etc.

broadrodent

Monkeypox (MPXV)

human, ape, monkey, rodent,

prairie dog, etc.

broadrodent, sciuridae

Cowpox (CPXV)

human, cat, catle, elephant,

rodent, rhinoceros, etc.

broadrodent

Camelpox

(CMLV)camelnarowunknown

Transmision Routes

VARV

•Transmited via droplets or aerosols.

•Initial infection ocurs in the nasopharynx or respiratory tract mucosa.

MPXV

•Zonotic transmision through African gophers and rodents (animal reservoirs).

•Transmision ocurs via direct contact with infected animals or their secretions.

CPXV

•Transmited via skin lesions or direct contactwith infected cats, rats, or tisues.

•Human-to-human transmision is not typicaly reported

Other Poxvirus Species

•Typicaly transmited via direct contactwith infected animals, tisues, or secretions.

Host and host specificity

Source: Literature research, Frost & SulivanSource: Literature research, Frost & Sulivan

Clinical characteristics	Smallpox	COWPOX, VACCINIA, OR SIMILAR ORTHOPOXVIRUSES
Incubation period(Days) 7-19 2-4
Fever, Malaise, Headache Yes Yes
Lymphadenopathy No Yes
Lesion distribution Spread in a centrifugal pattern; frequently Commonly confined to the hands, face, and neck. appears on the palms and soles.
Lesion characteristics • Deep-seated, well-circumscribed lesions with a central umbilication. • Rash evolves gradually through stages: macule → papule → vesicle → pustule → crust. • Entire progression spans 2–4 weeks.

	Smallpox	COWPOX, VACCINIA, OR SIMILAR ORTHOPOXVIRUSES
Infectious agents Variola virus Cowpox virus, Vaccinia virus, Akhmetavirus
Endemicity • Eradicated worldwide; • Cowpox virus: Europe and the Caucuses • Possibility of reemergence through • Vaccinia virus: the Americas (Argentina, Brazil, Colombia); deliberate release (e.g., bioterrorism) Asia (Bangladesh, India) • Akhmetavirus: Georgia
Great Risk population None Travelers with direct contact with animals, particularly bovids.
Prevention method • Vaccination • Avoid diseased agricultural bovids. • Use appropriate personal protective equipment (PPE).

Overview of Orthopoxvirus

Risk, Endemicity, and Prevention

Clinical Presentation

Source: Literature research, Frost & Sulivan

Overview of Orthopoxvirus

Diagnostic Methods

Therapy and

Prophylaxis

Prophylactic Vacination:

•VACV vacines are available but have significant adverse reactions.

•Post-9/11, certain populations (e.g., military, healthcare workers) in

the USA were vacinated with VACV.

•New third-generation vacines like MVA and LC16m8 (licensed in

Japan) are being developed with fewer side efects.

•MVA-based vacine (IMVAMUNE) has shown progres in clinical

trials, providing efective protection even after OPV exposure.

Chemotherapy:

•Cidofovir:

•A nucleoside phosphate inhibitor of viral DNA polymerase.

•Efective against OPV but limited by kidney toxicity and the

ned for intravenous administration.

•Derivative CMX001 is oraly bioavailable and les toxic.

•ST246:

•Inhibits OPV exit from infected cels by targeting the F13L

envelope protein.

•Efective post-symptom onset in animal models.

•Combined vacination and ST246 administration induce

protective imune responses.

•Sucesfuly used to treat severe eczema vacinatum in a

child.

•Combination Therapy:

•CMX001 and ST246 showed synergistic efects in

experimental treatments.

Pasive Imunisation:

•Imunoglobulin preparations (VIG) recomended for complications

asociated with vacination, limitedglobal availability of VIG.

Source: Literature research, Frost & Sulivan

112 100 74 38 19 4 2022年6月 2022年8月 2022年10月 2022年12月 2023年2月 2023年4月

Acumulated Number of Confirmed Cases and Deaths of

Monkeypox

•AcordingtoWHOdatadisclosure,asofApril4,2023,therehavebenatotalof86,838confirmedcasesworldwide,

including112confirmedeaths.

•AcordingtoWHOdatadisclosure,asofMarch28,2023,therehavebenatotalof24confirmedcasesofmonkeypox

inChina,withnodeathsreported.

Acumulated Number of Confirmed Casesof

Monkeypox worldwide

Source: WHO, Frost & Sulivan

Acumulated Confirmed Deathsfrom

Monkeypox worldwide

Note: Data for April 2023 as of April 4, 2023

5,655

50,566

77,042

84,102

86,270 86,838

2022年6月2022年8月2022年10月2022年12月2023年2月2023年4月

WHO recommends high-risk populations to receive primary preventive vaccines
• Men who are homosexual, bisexual, or have sexual relations with multiple sexual partners • Individuals with multiple temporary sexual partners • Sex worker • Laboratory personnel responsible for handling smallpox virus • Clinical laboratories and medical staff conducting monkeypox diagnostic tests • Members of the epidemic response team

Recomended Monkeypox vacine by WHO and Chinese CDC for

Disease Control and Prevention

Source: WHO, Chinese CDC, Frost & Sulivan

WHO

•Itisrecomendedthatcasecontactsreceivethepostexposure

prophylaxisvacine(PEPV)within4daysaftertheirfirstcontact

(upto14daysifasymptomatic);

•Thevacinationplanshouldincludecontinuoustrackingand

monitoringofcontacts,stronginformationdisemination,asound

adversedrugreactionmonitoringsystem,idealyacompaniedby

datacolectiontolsandstandardizedprotocolsforconducting

vacineficacyresearch,furtherensuringvacinesafety,and

providingefectivedatasuportforsubsequentexperiments.

•Whethertousemonkeypoxvacineshouldbebasedona

comprehensiveasesmentofindividualrisksandbenefits;

•Atpresent,large-scalevacinationagainstmonkeypoxisnot

recomended.Thelevelofexposureriskmayvarybypopulation,

andinsituationswherevacinesuplyislimited,countriescan

usexposurerisklevelstodeterminepriority;

Chinese CDC

•Duetotherelativelylimitedprevalenceofmonkeypox

inpreviousareas,andthefacthatmonkeypox

infectionisaselflimitingdiseasewithusualymild

clinicalsymptoms,comprehensivepreventionand

controlmeasuresmainlyfocusedonmanagingthe

sourceofinfectionaregeneralyadoptedfor

monkeypoxprevention.Chinacurentlydoesnot

providewidespreadvacinationforthepopulation,

butspecificpopulationscanbepreventedthrough

vacination.

•Duetothecrosimunity,vacinationwithsmalpox

vacinecanpreventmonkeypox,andvacination

withsmalpoxvacinebeforexposurecanefectively

protecthepopulationfrominfection;Within2weks

afterexposure,especialywithinthefirst4daysof

vacination,about85%ofindividualscandevelop

imunityandaleviatetheseverityofsymptoms.

High-risk population

Transmission routes

Overview of Chickenpox

•Chickenpox is an acute systemic infectious disease caused by the varicela-zoster virus (VZV). In imunocompetent

children, chickenpox is typicaly a benign, self-limiting ilnes; however, it tends to be more severe when it ocurs in

adults.

Symptoms

•Typicaly, after exposure to VZV for 14-16

days (range: 10-21 days), patients may

develop the chickenpox rash. One to two

days before the rash apears, patients

may experience fever, fatigue, malaise,

los of apetite, and headache, with

ocasional mild abdominal pain. These

symptoms usualy resolve on their own 2-

4 days after the rash apears.

InfantChildren

Adult

Pregnant

women

Imunocompromised

Individuals

Chickenpox is highly contagious, with the highest

infectivity ocuring during the prodromal phase and the

early stages of skin lesion apearance. It is transmited in

the folowing ways:

•Through inhalation of infected airborne droplets or

aerosolized particles, which infect the mucous

membranes (usualy the nasopharynx).

•Direct contact with the virus, such as through broken

skin.

•Although chickenpox is usualy self-limiting, it can be acompanied by

serious complications, typicaly caused by VZV itself or secondary bacterial

infections. Non-skin complications afecting the central nervous system

include conditions with a generaly god prognosis, such as cerebelar

ataxia, as wel as more severe conditions with a porer prognosis, such as

encephalitis.

•In rare cases, these complications may lead to death, particularly in

imunocompromised individuals. The most comon complication in

children is secondary bacterial infection, whereas in adults, the most

frequent complication is pneumonia (usualy viral pneumonia).

Complication

资料来源：文献资料，弗若斯特沙利文分析

Chickenpox prevention

Treatment and Prevention of Chickenpox

•Mild cases of chickenpox require only routine treatment. However, for patients with diseminated chickenpox and those

at high risk of severe disease, antiviral therapy and post-exposure prophylaxis (using antiviral medications or imune

globulin) are the primary treatment options.

•The cost of the chickenpox vacine is relatively low compared to the expenses of treating the disease, making it an

economical choice that can efectively reduce individual financial and disease burdens. Vacination is the most efective

method for preventing chickenpox, making it especialy necesary and urgent to use the chickenpox vacine for

prevention.

Imune globulinRoutine Treatment

Chickenpox treatment

•For high-risk individuals

susceptible to severe

chickenpox, post-

exposure prophylaxis

with VZV imune

globulin is an option.

However, VZV imune

globulin is expensive

and is not widely

available in many parts

of the world.

Antiviral therapy

•Imunocompromised

individuals and patients

with severe complications

generaly require

intravenous antiviral

medications.

•In imunocompromised

children, post-exposure

prophylaxis with oral

antiviral medications, such

as acyclovir, can also

safely and efectively

prevent secondary

chickenpox infections.

•Mild cases of chickenpox

only require symptomatic

treatment. It is important

to relieve itching and

avoid scratching to

prevent secondary

bacterial infections.

•For patients with severe

itching, options include

wet compreses,

systemic antihistamines,

or oatmeal baths to help

sothe the skin.

•Since chickenpox is highly

contagious and primarily spreads

through respiratory droplets and

direct contact, it has a high infectivity

rate, and people are generaly

susceptible. Chickenpox can ocur

year-round, with peak incidence in

winter and spring, making prevention

especialy important.

•Curently, vacination is the only

efective method for preventing

chickenpox and plays a critical role in

controling outbreaks and epidemics.

Source: WHO, Research paper, Frost & Sulivan

1	Overview of the human vaccine market

2	Overview of respiratory system vaccines

1.1	Overview of the Influenza Vaccine Market

1.2	Overview of the pneumococcal vaccine market

1.3	Overview of respiratory syncytial virus vaccine market

3	Overview of viral vaccines

3.1	Overview of the human rabies vaccine market

3.2	Overview of the zoster vaccine market

3.3	Overview of the broad spectrum orthopoxviral vaccine

3.4	Overview of the varicella vaccine

3.4	Overview of the tetanus vaccine

Transmission routes

Clinical manifestation

Overview of Tetanus

•Tetanus is an acute specific infection caused by the entry of Clostridium tetani into the body through wounds.

•Tetanus is clasified into neonatal tetanus and non-neonatal tetanus. China eliminated neonatal tetanus in 2012;

however, non-neonatal tetanus remains a serious public health isue.

Pathogenesis

•When Clostridium tetanispores enter

body tisues, they develop into

vegetative forms in an anaerobic

environment. These forms proliferate

extensively and release tetanospasmin,

trigering tetanus. Comon causes

include:

Clostridium tetani is an obligate anaerobe that is widely distributed in

nature, found in dust, soil, and human or animal feces. It primarily

enters the body through skin or mucosal wounds, most comonly in:

Source: 非新生儿破伤风诊疗规范（2019 年版）, Frost & Sulivan

Ahistoryofskin

ormucosal

injuryordamage

(suchasanimal

bites,injectionof

drugs,childbirth,

orabortion)

Ahistoryofbacterial

infectionintheskin,

mucosa,orsoft

tisues(suchas

chronicotitismedia,

chronicsinusitis,

periodontalinfection,

perianalinfection,

etc.)

Ahistoryof

gastrointestinal

tractinjury(such

gastrointestinal

surgeryor

perforation)

The incubation period for non-neonatal tetanus is typicaly 3–21

days, though it can be as short as 1 day or, in rare cases, extend

to over six months. The clinical manifestations of non-neonatal

tetanus are clasified into thre types:

✓Generalized Tetanus: Characterized by profuse sweating,

arhythmias, unstable hypertension or hypotension, and fever.

✓Localized Tetanus: Involves tonic and spasmodic muscle

contractions in a single limb or a specific area near the wound.

✓Cephalic Tetanus: Presents with dificulty swalowing and

cranial nerve paralysis, often acompanied by trismus

(lockjaw).

✓Patients with trauma or burn injuries

✓Newborns delivered in unsanitary conditions

✓Cases involving inadequately sterilized surgical

instruments。

Existing Challenges

• There are issues within China’s tetanus immunization system, as active immunization is administered by local preventive clinics, while passive immunization is handled by hospital emergency departments, creating a degree of disconnection between the two. • The use of Tetanus Antitoxin (TAT) or Tetanus Immunoglobulin (TIG) results in substantial waste of limited medical resources and, in some cases, the inappropriate use of TAT poses greater medical risks than tetanus itself. • Due to inadequate understanding of tetanus, many healthcare providers inform patients that immunoprophylaxismust be received within 24 hours post-injury to be effective, and some facilities even refuse immunoprophylaxisto patients if more than 24 hours have passed since the injury. • Furthermore, due to limited awareness of passive immunization, many physicians believe that patients will not develop tetanus after receiving TAT or TIG.

Tetanus Prevention Measures and Existing Chalenges

•Based on studies on various wound exposures and misconceptions in imunoprophylaxis, proper wound care and

vacination are crucial in preventing tetanus infection.

•Curently, there are certain isues within China’s tetanus vacination system; aditionaly, clinical standards for the use

of tetanus preparations in preventive treatment are not fuly standardized. As a result, there is a general lack of

uniformity in preventive measures, leading to inconsistencies in tetanus prophylaxis practices.

Wound management

Prevention Measures

Imunoprophylaxis

•Tetanus prevention primarily relies

on antibodies and can only be

achieved through primary or

secondary prevention.

•Primary Prevention (Active

Imunization): Involves

administering a vacine containing

tetanus toxoid (T) to induce

acquired imunity in the body.

•Secondary Prevention (Pasive

Imunization): Involves introducing

imune efectors, such as Tetanus

Antitoxin (TAT) or Tetanus

Imunoglobulin (TIG), into the body

to provide imediate imunity.

•Wounds are categorized based on

exposure as folows: (1) clean

wounds, (2) unclean wounds, and

(3) contaminated wound

•Wound management measures:

(1) For wounds with heavy

bacterial contamination and debris,

wound debridement is

recomended. (2) Wound

irigation is time-sensitive and

should be performed as son as

posible. (3) In some cases,

patients should consider receiving

oral penicilin antibiotics.

TAT or TIG.

Source: 中国破伤风免疫预防专家共识, Frost & Sulivan

Vaccine Type	Common Classification	Indications	Target Population	Representative Manufacturers

Clasification of Tetanus Vacines

Tetanus Vacine

(Monovalent)

Adsorbed Tetanus Vacine•Used to prevent tetanus

Primarily for individuals at

high risk of injury, pregnant

women in ned of boster

doses, as wel as newborns

and postpartum women.

•Olymvax

•Wuhan institute of biological

products

Multivalent

Vacines

Adsorbed Diphtheria-

Pertusis-Tetanus

Combination Vacine

•For boster imunization of

diphtheria, pertusis, and tetanus

in children who have completed

the primary imunization series

Children under 12 years old

•Wuhan institute of biological

products, etc.

Acelular Pertusis Diphtheria-

Tetanus Combination Vacine

•For prevention of diphtheria,

pertusis, and tetanus

Children aged 3 months to 6

years

•Wuhan institute of biological

products

•Beijing institute of biological

products

•GSK Pharmaceuticals

•Chengdu institute of biological

products

•Sanofi

•Changchun institute of biological

products, etc.

Acelular Pertusis Diphtheria-

Tetanus-Influenza Type B

Vacine

•For prevention of diphtheria,

tetanus, pertusis, Haemophilus

influenzae type B infections, and

related respiratory infections

Infants and todlers 3 months

and older

•MinhaiBiotech,

•Sanofi

•GSK Pharmaceuticals, etc

Acelular Pertusis Diphtheria-

Tetanus-Haemophilus

Influenzae Type B and

Influenza Vacine

•For prevention of diphtheria,

tetanus, pertusis, Haemophilus

influenzae type B infections, and

influenza-related respiratory

infections

Infants and todlers 2 months

and older

•Sanofi

•GSK Pharmaceuticals, etc.

Diphtheria-Tetanus-Pertusis-

Polio-Haemophilus Influenzae

Type B-Hepatitis B Vacine

•For prevention of diphtheria,

tetanus, pertusis, polio,

Haemophilus influenzae type B

infections, and hepatitis B

Infants and todlers 6 weks

to 4 years

•Sanofi, Merck Sharp & Dohme

Co., Inc.

Source: Research paper, Frost & Sulivan

Confirmation

1.Acording to WHO, there are around a bilion cases of seasonal influenza anualy, including aproximately 3 to 5

milion cases of severe ilnes that led to aproximately 290,000 to 650,000 respiratory deaths anualy.

2.Whole-virion inactivated influenza vacine variant involves cultivating the influenza virus and subsequently inactivating

it using heat or chemical methods.

3.IPD has a notably high mortality rates in children, particularly in low-and midle-income countries, where the mortality

rate for sepsis asociated with IPD can reach up to 20%, while that for meningitis can be as high as 50%.

4.Curently, PCV13 are used in infants and children and PSV23 are used in people aged 50 years and above or people

over 2 years old with increased infection risks.

5.The incidence of herpes zoster in China increased from 7.0 milion in 2019 to 7.7 milion in 2023. The global incidence

of herpes zoster also increased from 31.0 milion in 2019 to 40.8 milion in 2023.

6.Initialy concentrated in parts of Central and West Africa, the virus began to spread more widely, with outbreaks

reported in several countries acros Europe, North America and Asia. Acording to WHO, betwen January 1, 2022

and November 30, 2024 there had ben a total of 117,663 confirmed cases of monkeypox worldwide, including 263

confirmed deaths.

7.Monkeypox cases also emerged sporadicaly in China, with a total of 951 confirmed cases betwen September 2023

to November 2024.

8.In terms of production revenue, the Clas I vacine market in China increased from RMB51.4 bilion in 2019 to

RMB92.5 bilion in 2024, at a CAGR of 12.5%. Driven by increased awarenes and ability to pay and introduction of

new vacines, particularly with the anticipated increase in the manufacturing of Clas I vacines in the coming years,

the Clas I vacine market in China is expected to reach RMB324.4 bilion in 2033, at a CAGR of 15.0% from 2024 to

2033.

9.China’s quadrivalent influenza vacine market has grown significantly. The total number of lot release increased from

9.7 milion in 2019 to 46.6 milion in 2024, at a CAGR of 36.8%.

10.Referencing a vacination coverage rate of 49.3% in al people aged 6 months and older in the U.S. during the 2022-

2023 season compared to an overal vacination coverage rate of 3.8% in China for the same year, there is

considerable rom for improvement in China.

Confirmation

11.The global influenza vacine market increased from US$5.3 bilion in 2019 to US$6.6 bilion in 2024, at a CAGR of

4.5%, and is estimated to further increase to US$12.7 bilion in 2033, at a CAGR of 7.5% from 2024 to 2033. The

global subunit influenza vacine market has gradualy increased from US$0.4 bilion in 2019 to US$0.5 bilion in 2024,

and it is estimated to further increase to US$1.2 bilion by 2033.

12.The PSV23 market in China, in terms of production value, was RMB1.8 bilion in 2019. Driven by the increase

awarenes of pneumonia awarenes after the COVID outbreak in 2020, the PSV23 market significantly increased to

RMB3.4 bilion in 2020, with the total number of lot release of PSV23 vacine also increased from 9.5 milion in 2019

to 17.4 milion in 2020. However, after the marketing of COVID-19 vacines in 2021, the market size and lot release of

PSV23 have declined, remaining at aproximately the same level as in 2019. The market of PSV23 in China

decreased to RMB1.2 bilion in 2024 and the total number of lot release decreased to 6.2 milion in 2024. However,

with the increased availability more advanced products in China, the PSV23 market in China is expected to grow in

the next few years, reaching RMB5.0 bilion in 2033, at a CAGR of 17.4% from 2024 to 2033.

13.The advantage and limitations of each vacine or vacine candidate largely depend on the technical design of the

vacines

14.As of June 19

, no RSV vacine had ben aproved by the NMPA. As of the same date, there were 14 RSV vacine

candidates under clinical development in China.

15.As of June 19

, there were thre RSV vacines aproved by the FDA, including two recombinant vacines and one

mRNA vacine. As of the same date, there were 22 RSV vacine candidates under clinical development outside China.

16.As of June 19

, there were eight marketed varicela vacines in China, al of which are live atenuated vacines. As of

the same date, there were two varicela vacine candidates under clinical development in China, both of which are live

atenuated vacines.

17.As of June 19

, there were six marketed single-component tetanus vacines in China, al of which were adsorbed

vacines. As of the same date, there were four single-component tetanus vacine candidates under clinical

development in China, al of which were adsorbed vacines.

18.As of the June 19

, no mpox vacine had ben aproved by the NMPA and there was one mpox vacine candidate

under clinical development in China. As of the same date, there were two mpox vacine aproved by the FDA, which

was a live atenuated vacine, and thre mpox vacines (one live atenuated vacine and two mRNA vacines) under

clinical development outside China.

Confirmation

19.The average biding prices for influenza vacines in China decreased from RMB126 per dose in 2022 to RMB125 per

dose in 2023, and further decreased to RMB93 per dose in 2024. In particular, the average biding price of split-virion

vacine droped significantly, from RMB122 per dose in 2022 to RMB119 per does in 2023 and further to RMB85 per

dose in 2024. However, influenza vacination rate in China increased from 2.5% in the 2021-2022 influenza season to

3.8% in the 2022-2023 influenza season. For the 2023-2024 season, while no oficial overal influenza vacination rate

is available, it is estimated that the influenza vacination rate in China remained relatively stable at 3.0% to 3.5%. In

2029, the influenza vacination rate is estimated to reach aproximately 9.0% to 9.5%, with an estimated average

price of aproximately RMB85 to RMB88 per dose. In 2033, the influenza vacination rate in China is estimated to

reach aproximately 15.0% to 15.5%, with an estimated average price of aproximately RMB80 to RMB85 per dose.

20.In China, varicela incidence shows a seasonal patern, with peaks from May to June and from October to January of

the folowing year. There were aproximately 516.6 thousand reported cases of varicela in China in 2024.

Table of Contents

Introduction to the definition and mechanism of action of vacines

Source: WHO, Frost & Sulivan analysis

Overview of the Circulation of Clas I Vacines in China

Source: Frost & Sulivan Analysis

Table of Contents

Source: Frost & Sulivan

Introduction to vacine types and design principles

Definition and Clasification of Inactivated Subunit Vacines

Sources: GAVI, Frost & Sulivan

Comparison Betwen Inactivated Subunit Vacines and Split

Vacines and Analysis of Technical Dificulties

Source: Frost & Sulivan

Production Proces of Inactivated Subunit Vacines

Source: Frost & Sulivan

Aplications and Clasification of mRNA Vacines

Source: Literature Review, Frost & Sulivan

Analysis of the mRNA Vacine Production Proces, Advantages,

and Chalenges

Source: Literature Review, Frost & Sulivan

Delivery Strategy for mRNA Vacines

Source: Literature Review, Frost & Sulivan

Overview of Subunit Vacines

Benefit:Type of Subunit vacine

Basic Design Proces:

1.Imunogenic subunit identification

2.Expresion and synthesis of subunit

3.Extraction and purification

4.Adjuvant adition or vector incorporation

5.Formulation and delivery

Overview of Polysacharide Conjugate Vacines

Production Complexity of Polysacharide Conjugate Vacines

1. Antigen Selection and Serotype Integration

2. Carier Protein Interference with Imune Response

3. Chalenges with Multivalent Vacines

4. Quality Control and Proces Optimization

Overview of recombinant vacines

Table of Contents

Source: Frost & Sulivan

Global Development History of the Vacine

Source: Frost & Sulivan

Vacines Aproved by FDA in 2019-2024

Source: FDA, Frost & Sulivan

China Human Vacine Market Size, 2019-2033E

Source: Anual Repot, Frost & Sulivan

China Human Vacine Market Size by Production Value, 2019-2033E

Global Human Vacine Market Size, 2019-2033E

Global Human Vacine Market Size, 2019-2033E

Source: Anual Repot, Frost & Sulivan

Global Vacination Situation, Chalenges and Neds

Neds of Developing

Countries

Source: Literature Review, Frost & Sulivan

Table of Contents

Vacines Aproved by NMPA in 2019-2024

Source: NMPA, Frost & Sulivan analysis

Vacines Aproved by NMPA in 2019-2024

Source: NMPA, Frost & Sulivan analysis

Vacines Aproved by NMPA in 2019-2024

Source: NMPA, Frost & Sulivan analysis

Introduction to the ful lifecycle proces of Chinese vacines and

average years of research and development

Source: Frost & Sulivan

Comparison of Vacination Coverage in China, United States and

GAVI Countries

Source: Frost & Sulivan

Note:

Regulations in Vacine Value Chain in China

Source: Government Anouncement, Frost & Sulivan analysis

Entry Bariers of Human Vacines Market in China(1/2)

Source: Frost & Sulivan Analysis

Entry Bariers Human Vacines Market in China(2/2)

Source: Frost & Sulivan Analysis

Regulations of Vacine Market in China -I

Source: Government Anouncement, Frost & Sulivan analysis

Regulations of Vacine Market in China -I

Source: Government Anouncement, Frost & Sulivan analysis

Regulations of Vacine Market in China –I

Source: Government Anouncement, Frost & Sulivan analysis

Regulations of Vacine Market in China –Ⅳ