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TABLE 6.2 Timeline of approved vaccines for infectious diseases by product type and year.
Live attenuated organisms
Inactivated whole
organisms
Purified proteins,
polysaccharides, or
conjugates
Recombinant protein,
genetically engineered,
vectored Nucleic acid-based
1700s
(1 vaccine)
Smallpox (1798)
1800s
(4 vaccines)
Rabies (1885) Typhoid (1896)
Cholera (1896)
Plague (1897)
1900e1950
(7 vaccines)
Tuberculosis (bacillus
CalmetteeGuérin, 1927)
Pertussis (1926) Diphtheria toxoid (1923)
Yellow fever (1935) Influenza (1936) Tetanus toxoid (1926)
Rickettsia (1938)
1950e1999
(32 vaccines)
Polio (oral, 1963
discontinued 2000)
Polio (injected, 1955) Anthrax secreted proteins
(1970)
Hepatitis B surface antigen
recombinant (1986)
Measles (1963) Rabies (human cell culture,
1980)
Meningococcus
polysaccharide C (1974)
Lyme OspA (1998e2002 when
withdrawn for lack of market)
Mumps (1967) Japanese encephalitis
(mouse brain, 1992)
Pneumococcus
polysaccharide (14-valent,
1977)
Cholera (recombinant toxin B,
1993)
Rubella (1969) Rabies (chick embryo cell,
1997)
Meningococcus A and
bivalent AC (1978)
Hepatitis B (plasma derived)
(1981)
6. Introduction to vaccines and adjuvants186
II. Vaccines
Adenovirus (1980) Tick-borne encephalitis
(1981)
Pneumococcus
polysaccharide (23-valent,
1983)
Typhoid (Salmonella TY21a
oral, 1989)
Cholera (WC-rBS, 1991) Haemophilus influenzae type
B polysaccharide (1985)
Varicella (1995) Hepatitis A (1995) H. influenzae type B
conjugate (1987)
Rotavirus reassortants
(1998)
Intranasal influenza
(2003e16 then 2018)
Acellular pertussis (1991)
Cholera (attenuated) (1994) Typhoid (Vi) polysaccharide
(1994)
Cold-adapted influenza
(1999)
Meningococcal conjugate
(group C) (1999)
2000 to 2023
(37 vaccines)
Rotavirus (attenuated and
new reassortants, 2006)
Japanese encephalitis (Vero
cell, 2009)
Pneumococcal conjugates
(heptavalent) (2000)
Human papillomavirus
recombinant (quadrivalent)
(2006)
COVID-19 mRNA
Vaccine (nucleoside
modified, Pfizer-
BioNTech, 2020)
Herpes zoster (2006-not
available as of 2020)
Cholera (whole cell only,
2009)
Meningococcal conjugates
(quadrivalent) (2005)
Human papillomavirus
recombinant (bivalent) (2009)
COVID-19 mRNA
vaccine (nucleoside-
modified, Moderna
2020)
Smallpox (Vaccinia) vaccine,
live (2007)
Influenza monovalent
pandemic (2009)
Pneumococcal conjugates
(13-valent) (2010)
Meningococcal group B
bivalent (2013)
ZyCoV-D (DNA,
India, 2021)
Rotavirus monovalent
(2008)
Influenza cell-based (2007
EU and 2012 US)
Meningococcal CRM197
conjugates (quadrivalent)
(2010)
Influenza baculovirus HA
(2013)
Dengue tetravalent vaccine
(live, attenuated, Sanofi,
2015 Asia-2019 US)
In
fluenza intradermal (2014) Human papillomavirus
recombinant (9-valent, 2014)
(Continued)
Introduction 187
II. Vaccines
TABLE 6.2 Timeline of approved vaccines for infectious diseases by product type and year.dcont’ d
Live attenuated organisms
Inactivated whole
organisms
Purified proteins,
polysaccharides, or
conjugates
Recombinant protein,
genetically engineered,
vectored Nucleic acid-based
Modified Vaccinia Ankara
virus for smallpox/Mpox
(2019)
Influenza MF59-adjuvanted
(1997 in EU, 2015 in US)
Meningococcal group B (4
component reverse
vaccinology, 2015)
Dengue tetravalent vaccine
(live, attenuated, Takeda,
2022 EU)
Cholera (serogroup 01 oral,
2016)
Herpes zoster (AS01b
adjuvanted, 2017)
Hepatitis B (CpG 1018
adjuvant, 2017
Ebola Zaire Vaccinedlive
attenuated rVSV containing
ZEBOV envelope glycoprotein
(2019)
Ebola Ad26.ZEBOV and MVA-
BN-Filo (2020)
*COVID-19 Vaccine,
Adjuvanted (Matrix M, 2022)
ChAdOx1 nCoV-19 vaccine
(AZD1222)
Ad26.COV2.S COVID-19 single
dose vaccine (2021- no longer
available as of 2023)
RTS,S/AS01 (RTS,S) Malaria
Vaccine (WHO 2022)
R21/Matrix-MÔ (select African
countries 2023)
Respiratory Syncytial Virus
RSVPreF3 recombinant vaccine
60þ (2023)
Respiratory Syncytial Virus
bivalent, recombinant
vaccinedmaternal
immunization and 60þ (2023)
Adapted from Plotkin (2014) and Gerberding and Haynes (2021). Not all-inclusive, and primarily focused on US- and EU-approved vaccines.
6. Introduction to vaccines and adjuvants188
II. Vaccines
technologies are still being used with success, there has been a shift to recombinant immuno-
gens (antigens), vectored vaccines, virus-like particles (VLPs), and nucleic acid vaccines.
Newer, yet to be approved technologies include viral antigen-presenting cells (e.g., dendritic
cells), T cell-based vaccines, and bacterial vectors (Pollard, 2021). Killed or attenuated live
vaccines, vectored, VLP, and some nucleic acid vaccines possess characteristics in common
with invading organisms and are, therefore, inherently immunogenic, while purer recombi-
nant or polysaccharide antigens often require the inclusion of adjuvant(s) to provide the im-
mune defense-trigger ing signals that have been lost in the antigen design and/or purification.
Adjuvants, from Latin adjuvare, to help or aid, are compounds added to enhance the
magnitude and direction of immune responses to vaccine antigens, which have a history
that lagged, but paralleled advancements in the design of antigens. Investigators sought
ways to improve the immune responses to antigens, beginning in 1925 with Gaston Ramon,
who observed that immune responses to diphtheria toxoid in horses used for the production
of antitoxin (antitoxin antibodies) were stronger in animals that developed abscesses at the
injection site. To incite an abscess surrogate, he mixed toxoid with substances including
tapioca, starch, agar, lecithin, an emulsion of oil, or breadcrumbs (Ramon, 1925, 1955)in
an attempt to enhance antitoxin production. Approximately 1 year later, Glenny showed
that aluminum salts significantly increased the effectiveness of diphtheria toxoid, the vaccine
antigens used to protect against diphtheria in challenged guine a pigs (Glenny, 1926). It is
notable that aluminum-based adjuvants were the only ones used in approved vaccines for
approximately 70 years but the number of adjuvants used in approved vaccines has
expanded in the last 25 years or so. Table 6.3 shows the timeline and adjuvant composition
of US approvals of example adjuvanted vaccines. In general, Europe has tended to be an
earlier adopter of adjuvants than the US.
The fastest moving adjuvanted vaccine disease area is, perhaps unsurprisingly, COVID-19.
EU-approved and experimental adjuvanted COVID-19 vaccines are reviewed by Castrodeza-
Sanz et al. (2023) and the WHO COVID-19 vaccine tracker and landscape webpage (last
updated March 30, 2023) shows 183 and 199 candidates were in clinical and nonclinical
testing, respectively, at that time.
The successes of the COVID-19 pandemic vectored and mRNA vaccines has expanded
testing of the technologies for other infectious disease targets as well as for therapeutic vac-
cines. Like preventive vaccines, therapeutic vaccines are based on equally heterogeneous im-
munogens including self- and non-self-proteins (peptide/protein, DNA, and mRNA
vaccines), vector-based vaccines (bacterial vector vaccines, viral vector vaccines, and yeast-
based vacci nes) and cell-based vaccines (autologous cells, allogeneic cells, dendritic cells,
and genetically modified cells) as well as combinations of these approaches (Tian, 2022).
Because therapeutic targets are often complex and challenging, an adjuvant or a combination
of adjuva nts and/or immunostimulatory compounds may be needed.
Adjuvants in vaccine formulations can increase the magnitude of the immune response;
increase the breadth of the immune response; bias the immune response toward a cellular
(Th1) response or humoral (Th2) response; allow for fewer administrations and/or lower an-
tigen doses; increase immunogenicity in low-responding individuals (very young, elderly,
immunosuppressed), overcome antigenic competition, impact the durability of responses,
and re-direct the immune response in chronic infections, cancer, and chronic diseases
(Reed, 2009). Major advances in understanding the mechanism(s) of action of adjuvants
Introduction 189
II. Vaccines
TABLE 6.3 Timeline and adjuvant composition of US-approved adjuvanted vaccines.
Adjuvant Composition Formulation Vaccines Year
US-licensed adjuvanted pediatric vaccines
Aluminum One or more of the following: aluminum
hydroxyphosphate sulfate (AAHS),
aluminum hydroxide, aluminum
phosphate, potassium Alum
Various/Aqueous
(PBS-based)
Anthrax (BioThrax), DT, DTaP (Daptacel),
DTaP (Infanrix), DTaP-IPV (Kinrix), DTaP-
IPV (Quadracel), DTaP-HepB-IPV
(Pediarix), DTaP eIPV/Hib (Pentacel),
Hep A (Havrix), Hep A (Vaqta), Hep B
(Engerix-B), Hep B (Recombivax), HepA/
Hep B (Twinrix), HIB (PedvaxHIB), HPV
(Gardasil 9), Japanese encephalitis (Ixiaro),
MenB (Bexsero, Trumenba), Pneumococcal
(Prevnar 13, Vaxelis), Td (Tenivac), Td
(Mass Biologics), Tdap (Adacel), Tdap
(Boostrix)
1930ePresent
US licensed adjuvanted adult vaccines
MF59 Oil in water emulsion composed of
squalene
Emulsion-based TIV (Fluad) (for adults aged 65 or older) 2015
AS01B MPL and QS-21 (extracted from the
Chilean soapbark tree)
Liposomes with
dioleoyl
phosphatidylcholine
and cholesterol
RZV (Shingrix) (for adults aged 50 or older) 2017
CpG 1018 CpG, a synthetic form of DNA that mimics
bacterial oligodeoxynucleotide and viral
genetic material
PBS-based Hep B (Heplisav-B) (for adults aged 18 or
older)
2017
Matrix M Mixture of Fractions A and C from Chilean
soapbark tree
Phospholipids,
cholesterol, buffer
Novavax COVID-19 Vaccine, Adjuvanted 2022
CpG 7909 Oligodeoxynucleotide þ aluminum salt Aluminum hydroxide-
adsorbed
Anthrax (Cyfendus) for postexposure
prophylaxis
2023
AS01E MPL and QS-21, a natural compound
extracted from the Chilean soapbark tree
Liposomes with
dioleoyl
phosphatidylcholine
and cholesterol
RSVPreF3 vaccine (Arexvy) 2023
6. Introduction to vaccines and adjuvants190
II. Vaccines
Approved, but not commercially available in US
AS04 MPL þ aluminum salt VLPs þ MPL adsorbed
onto Alum, PBS based
HPV (Cervarix)dnot available in since
2016 in US for commercial reasons but is
approved in China, Europe, the
Netherlands, and the U.K.
2009
AS03 a-Tocopherol, squalene, and polysorbate
80
Emulsion-based Monovalent Pandemic H5N1 Swine
Influenza A (Q-Pan H5N1) (for adults aged
18 or older)
2013
Adapted from Nanishi (2020), O’Hagan (2020), and Reyes (2023).
Introduction 191
II. Vaccines
have been made in parallel with discoveries and understanding of PRRs. Adjuvants have his-
torically (O’Hagan, 2007 ) been categorized into delivery systems (e.g., aluminum salts, cal-
cium phosphate, tyrosine, liposomes, virosomes, emulsions, microparticles/nanoparticles,
Iscoms, virus-like particles) and immunopotentiators (e.g., MPL and synthetic derivatives,
MDP and derivatives, CpG oligonucleotides, alternative bacterial or viral componentsd
flagellin etc., lipopeptides, saponins, doub le stranded RNA, small molecule immune potenti-
ators such as Resiquimod). However, with the understanding of PRRs mechanisms of action,
adjuvants can also be categorized (Tizard, 2021) as DAMP-inducing (causing cellular damage
at the injection site), PAMP-inducing (resemble pathogens), and particulate adjuvants (parti-
cles optimized for ingestion and processing by antigen-presenting cells). Some adjuvants may
engage multiple PRRs, resulting in stronger immune activation (Kumar, 2011). Other adju-
vant technol ogies include molecular adjuvants in which ligands of known immunomodula-
tory receptors are directly fused to antigens (Sicard, 2020; Zhang, 2023), genetic adjuvants,
i.e., immunomodulatory proteins expressed along with nucleic acid- or vector-expressed an-
tigens (Sabbaghi, 2021; Xie, 2023), decorat ed LNPs that enable the selective delivery of mRNA
to specific cell types via targeting molecules (Wang, 2023), and LNPs incorporating various
ionizable lipids (lipidoids) that enhance the innate adjuvanticity that has been reported for
earlier generation LNPs (Han, 2023; Li, 2023) and can modify tolerability/toxicity (Bitounis,
2024). Many vaccine adjuvants that are potent and tolerated in nonclinical models have failed
in clinical trials because of tolerability/safety issues. The goal is to find the right balance of
immunostimulation/inflammation that enhances immune responses without untoward
side-effects.
Most vaccines are administered by the intramuscular route, followed by the subcutaneous
route. However, the delivery of vaccines to specific immunological compartments is also a
very active area of research. Mucosal, intradermal, inh alation, intranasal, sublingual, and
oral routes are being studied, along with novel devices (nebulizers, sprayers, transdermal
patches, microneedles, electroporation, etc.), as are unique formulations (dry powder.
controlled-release, and fast-dissolving). Within a common regulatory framework (Chapter
7), the strategies for nonclinical evaluations (Chapters 7 and 8) are disease, antigen, adjuvant,
route, formulation, and device-specific.
Given the diversity of approaches, nonclinical testing programs usually include in vitro
and ex vivo studies, and as well as in vivo studies in one or more species. As discussed in
Chapters 7 and 8, programs must be tailored for each disease, vaccine, and adjuvant. A com-
mon denominator to any nonclinical program is the selection of appropriate species ba sed on
their ability to react to the vaccine/adjuvant in a way that is qualitatively similar to humans,
i.e., the primary pharmaco logy. Depending upon the disease target, primary pharmacology
studies usually consist of demonstrating the vaccine proof-of-concept of immunogenicity in
healthy nonclinical species and protection or therapy in established animal models of the dis-
ease, if available. In the case of certain diseases, there are controlled human infection models
(CHIMs) that are extremely valuable for the demonstration of immunogenicity and protec-
tion, understanding disease pathogenesis, and candidate selection (Gordon, 2017). Good Lab-
oratory Practice (GLP) toxicology studies that assess local and systemic tolerability/toxicity;
and reproductive and developmental toxicity studies, if women of childbearing potential or
pregnant women are target populations, are required. The need for additional (e.g., safety
pharmacology, biodistribution, genotoxicity, etc.), or special studies (e.g., neurovirulence)
6. Introduction to vaccines and adjuvants192
II. Vaccines
is determined on a case-by-case basis, and information on the vaccine mechanism of action is
beneficial as is information on clinical correlates or surrogates of protection.
Impacts of current vaccines on human health
“That vaccines have had a greater effect on [reducing] mortality than any measure besides
clean water has become a cliché” (Plotkin, 2008). However, “no other modality, not even an-
tibiotics, has had such a major effect on mortality reduction and population growth” (Pollard,
2007). Preventive vaccines effectively protect people against infectious diseases, promote bet-
ter health and quality of life on local and global levels, are highly cost-effective versus drugs
and other treatments, and have an excellent cum ulative safety record (Stratton, 2011).
Smallpox was declared eradicated by the World Health Assembly in 1980 and, per the US
Centers for Disease Control and Prevention (CDC), polio has been eliminated in the Western
world and has decreased worldwide by 99% (CDC, December 1, 2023). According to the
WHO (August 9, 2023), measles vaccination prevented 56 million deaths between 2000 and
2021. However, an estimated 128,000 measl es deaths occurred globally in 2021, mostly in un-
vaccinated or under-vaccinated children less than 5 years of age. Globally, approximately
83% of the world’s children received one dose of measles vaccine through health services
by their first birthday in 2022, the lowest percentage since 2008, another impact of the
SARS-CoV-2 pandemic.
The CDC (April 20, 2023) states that 4 million deaths worldwide are prevented by child-
hood vaccination every year and that more than 50 million deaths could be prevented
through immunization between 2021 and 2030. By 2030, it is estimated that just improved
measles and hepatitis B vaccination camp aigns could save almost 19 million and 14 million
lives, respectively. The Vaccine Impact Modeling Consortium, which was established in 2016,
studied 10 pathogens (Haemophilus influenzae type b, hepatitis B, human papillomavirus, Jap-
anese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Strepto-
coccus pneumoniae, and yellow fever) across 112 countri es from 2000e30 (Toor, 2021). The
study showed that 97 million lives were estimated to be saved in a pre-COVID-19 world
and that, although the pandemic has disrupted vaccination efforts, the benefits of vaccination
were clear and support continued efforts to sustain and expand global vaccine coverage.
The science (and business) of vaccinology
In general terms, vaccinology is the science of vaccine development and how the immune
system responds to vaccines, which is well reviewed in a recent article by Pollard (2021) and
presented in the context of COVID-19’s impact on the field by Rappuoli (2021). Vaccinology
was defined in 2003 as “a new field of microbiology and immunology” that has evolved,
“that comprises not only vaccine development but also the use of vaccines and their effects
on public health” (Plotkin, 2003 ) and in 2016 as “the science of vaccines, and historically in-
cludes basic science, immunogens, the host immune response, delivery strategies and tech-
nologies, manufacturing, and clinical evaluation” (Barret, 2016). Barrett (2016) further
comments that “in the 21st century vaccines will also potentially make significant contribu-
tions to the control of non-infectious diseases.” Barret’s prediction has been borne out based
The science (and business) of vaccinology 193
II. Vaccines
on relatively recent data from Pharmaceutical Research and Manufacturers of America
(PhRMA) and Vaccines Europe.
PhRMA (2020) reported that there were 258 vaccines in development by US companies:
125 for infectious diseases, 108 for cancer, 14 for allergies, 3 for autoimmune diseases, and
2 for Alzheimer’s disease. Vaccines Europe (August 2023) reported that there were 103 vac-
cine candidates in the pipelines of their 15 members: 99 of which were preventive and 4 of
which were therapeutic. As of March 2023, for COVID-19 vaccines alone, the WHO docu-
mented 183 vaccines in clinical testing and 199 in preclinical testing (WHO, March 30, 2023).
Althoughthere is variability in the figuresreported in various analyses, thepreventive vaccine
market accounted for 39.45 billion USD in 2020 and is estimated to be 69.0 billion USD by 2030
(PMI, 2023) and the therapeutic vaccines market was valued at USD 27.4 billion in 2020 and is
projected to reach USD 103.23 billion by 2028 (VMR, 2023). However, vaccine development re-
quires very high levels of capital investment, constant and intensive investment in
manufacturing, facilities, and personnel to maintain state-of-the-art research, safety assessment,
and compliance with robust regulatory requirements. While market sizes sound attractive, the
probabilities of success (POS) for a new infectious disease vaccine at development phase transi-
tions has been estimated at 40%e50% for the preclinical to Phase 1 stage (Gouglas, 2018), and at
76.8%for the Phase 1 to2 transition, 58.2%at thePhase 2to 3 transition, and at 85.4% fromPhase 3
to approval, yielding an overall POS of 33.4% (Wong, 2019). The 2018Gouglas et al.study, which
analyzed the WHO’s 11 priority epidemic infectious diseases at the time, found that the cost of
developing one epidemic infectious disease vaccine from nonclinical testing through the end of
Phase 2a, was 31e68 million USD (range 14e159 million USD) assuming no risk of failure. The
costs were substantially higher when the POS for the stage was factored in.
Total R&D costs have been estimated at 200 million to 500 million USD per successful vac-
cine (Plotkin, 2017) and 500 million to 1.5 billion USD (Gouglas, 2018). As an exampl e, the
number of Phase 2/3 trial subjects (Weinberg, 2012) can range from approximately 3000
(e.g., IPOL inactivated polio) to approximately 80,000 (e.g., Rotarix). Postlicensure risk man-
agement programs and pharmacovigilance monitoring are required so rare adverse events
can be captured.
While vaccines can be profitable, primarily based on sales in wealthy countries, they are
often low to no profit in middle-to low-income countries that may need the m most. This
two-market paradigm contributes to the selection of disease targets that vaccines companies
prioritize. The complex pressures on companies in the industry is reflected by such high-
profile companies as Novartis and Baxter divesting their vaccines business units in the last
decade. A threat to global health has been raised concerning the limited number of companies
engaged in vaccine R&D. The WHO Global Vaccine Market Report (2022) reports that,
although manufacturing capacity worldwide has increased, with the exception of COVID-
19 vaccine s, only 10 manufacturers provide 70% of vaccine doses. Just two or three
companies are the primary providers of several of the top 20 most widely used vaccines
(pneumococcal, human papilloma, and measles and rubella containing vaccines). SARS-
CoV-2 saw many companies jump into vaccines for COVID-19, as documented in the
WHO COVID-19 vaccine tracker and landscape (March 30, 2023). However, it is of note
that the first-wave CoVID-19 vaccine innovators were not big Pharma, but smaller entities
or subsidiaries (Moderna, BioNtech SE, Janssen, Oxford University) who had been working
on their respective vaccine platforms for other diseases.
6. Introduction to vaccines and adjuvants194
II. Vaccines
Vaccine platforms can accelerate development and approval of new vaccines
The Johns Hopkins Center for Health Security Report (2019) defined a vaccine platform as
follows: “a technology was defined as a platform if an underlying, nearly identical mecha-
nism, device, delivery vector, or cell line was employed for multiple target vaccines”. The
idea is that a vaccine platform can be used first to develop and approve one vaccine, then
be used interchangeably for other diseases by swapping out the disease-specific moiety(ies)
to enable efficient and cost-effective development, streamline regulatory approval, and com-
mercial manufacturing. Regulations pertaining to nonclinical considerations for vaccine plat-
forms are presented by Plitnick in Chapter 7.
Strategies for leveraging the information from studies performed with vaccines for other
indications for a new indication can be found in the COVID-19 vaccine Summary Basis of
Regulatory Action for vaccines approved in the US, the European public assessment reports
(EPARs) for the EU-approved vaccines, and the Medicines and Healthcare products Regula-
tory Authority (MHRA) Public Assessment Reports for those approved in the UK. As an
example, Tables 6.4 and 6.5 show the nonclinical progra m of studies submitted to EMA
(March 11, 2021) for COVID-19 Vaccine Moderna (mRNA-1273, Spikevax). A GLP-
compliant reproductive and developmental toxicology (DART) study in rats (not shown in
the table) was also conducted.
While the pharmacology studies utilized the vaccine candidate mRNA-1273, the majority
of the other studies required to support First-in-Human (FIH) clinical trials were conducted
with platform vaccines. Speci fically, biodistribution was assessed using mRNA-1647 (con-
tains 6 mRNAs encoding the full length Cytomegalovi rus (CMV) glycoprotein B, and the
pentameric glycoprotein H glycoprotein L (gL)/UL128/UL130/UL131A glycoprotein com-
plex) as a surrogate for mRNA-1273 (expressing prefusion Spike protein). Several GLP toxi-
cology studies had been performed with other mRNA vacci ne candidates based on the same
platform (Zika, CMV, human Metapneumovirus/Parainfluenza virus 3, CMV). Given the
availability of these data to support FIH studies, only one non-GLP repeat-dose toxicity study
was performed with the actual product (mRNA-1273). To support later development and fil-
ing, a GLP-compliant DART study with mRNA-1273 in female Sprague Dawley CD rats was
submitted. Pharmacokinetics (PK) studies supporting use of SM-102, the novel lipid in the
LNP, consisted of an intravenous PK study with SM-1 02 and bridging to PK studies conduct-
ed with SM-86, a similar PEG2000-lipid, based on both lipids having similar structures.
In vitro and in vivo genotoxicity studies were also conducted to support the use of SM-
102. The EPAR for Comirnaty (Pfizer/BioNTech, https://www.ema.europa.eu/en/
documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf; accessed
April 15, 2024) mRNA COVID-19 vaccine shows a somewhat different approach to their
nonclinical program.
There is no generic FDA or EMA guidance for data requirements for human vaccines pro-
duced using the same vaccine platform that has been used for an approved vaccine (see
Chapter 7 for current guidelines to be considered). However, EMA has published a guideline
(2022) on data requirements for vaccine platform technology ma ster files (vPTMF) for veter-
inary vaccines that could be a template for human vaccines. A 2023 joint position paper from
Vaccines Europe (March 30, 2023b), EFPIA (European Federation of Pharmaceutical Indus-
tries and Associations), and CEPI (Coalition for Epidemic Preparedness Innovations) makes
The science (and business) of vaccinology 195
II. Vaccines
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