vaccine

development
What is a vaccine?
Vaccines are biological products that generate vaccine history
acquired immunity to specific infectious diseases. The history of vaccine research is rich
with scientific breakthroughs.

1700s 1798 Edward Jenner coins the terms “vaccine” and

vaccines are saving lives “vaccination” as part of his work on a smallpox
vaccine.
The principal of vaccination is to train the immune 1800s 1800 Smallpox vaccination becomes
system to recognize and react to an infectious commonplace.
agent, and to induce an effective immune response. 1870s-80s Louis Pasteur develops first live bacterial
This ensures that the individual is protected against vaccine for chicken cholera and the first
the pathogen in the future. live viral vaccine for rabies.
1900s 1918 Spanish flu pandemic kills 25-50 million
Vaccines are critical in the prevention and worldwide.
control of infectious disease outbreaks. 1926-28 Developmet of tuberculosis, diphtheria,
tetanus and whooping cough vaccines.
The World Health Organization (WHO) states
that vaccines now prevent more than 20 1945 An inactivated influenza vaccine is licensed
in the US.
life-threatening diseases.
1950-60 First combination vaccines developed (DTP
Immunization prevents 2-3 million deaths – diphtheria, tetanus and whooping cough).
per year.
1952 Nearly 60,000 cases of polio are documented
in the US.
1955 First polio vaccine pioneered by Jonas Salk
is licensed in the US.
1961 An orally administered polio vaccine
The potential cost of developed by Albert Sabin is licensed in
the US.
illness avoided due to 1963 Measles vaccine is licensed in the US.

$63B
vaccinations from 2011-2020: 1974 Meningococcal polysaccharide vaccine is
licensed in the US.
1980 Smallpox is the first infectious disease
eradicated by vaccination.
1986 First genetically engineered vaccine
(hepatitis B) is developed.
2000s 2000s Measles and rubella are no longer endemic in
the US.
2006 Human papillomavirus vaccine (HPV) is
licensed in the US.
2009 Vaccines against 1009 H1N1 pandemic
strain and high-dose influenza vaccine are
licensed in the US. More than 12,000
Americans died during the H1N1
pandemic.

Haemophilus Pneumococcal
infections Rotavirus
influenzae type b
$27 B $24 B $12 B

Understanding the different types of vaccines

There are various different types of vaccines that are utilized to

fight against different infectious pathogens. Examples include:

Inactivated Toxoid Live-attenuated

Uses a dead form of A toxin produced A weakened form
a pathogen that has by the pathogen of the antigen that
been inactivated that causes a causes a disease is
using chemicals, disease is used. used to generate
heat or radiation. an immune
response.
Subunit, polysaccharide, conjugate mRNA
and recombinant Messenger ribonucleid acid (mRNA)
A certain piece of a pathogen, such as encoding a particular viral protein
a sugar, protein or capsid, is used to induces endogenous production of
generate an immune response. the protein in the recipient's cells.

vaccine development

There are several key stages involved in the development and approval of a new vaccine.
The specifics of each stage in this pipeline will differ according to the type of vaccine that is being developed.
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Phase: 1 2 3 4
Safety Efficacy Safety & Safety monitoring for
efficacy serious adverse events

Varies 2-4 years 6-8 years Approx 3 years Continuous

Traditional vs "new-era" vaccines

Under typical circumstances, the development of a new vaccine can take 10-15 years to
complete. In response to the COVID-19 global pandemic, this process has been accelerated
by carrying out specific stages in parallel with one another.
One outcome of this acceleration has been the rapid manufacturing, testing and emergency
use authorization (EUA) of mRNA-based vaccines. RNA-based vaccines are often referred to
as "new-era" or "next-generation" vaccines.
Note: Although the COVID-19 vaccines are the first examples authorized for human use,
scientists have been studying and manufacturing RNA-based vaccines for many years for
their potential use against infectious diseases and cancer.1

How does the development and

manufacturing of traditional vs mRNA-based
vaccines compare?
Let's take a look. This schematic summarizes the upstream and downstream production of
the cell-based inactivated influenza vaccine.2

WHO candidate virus

Seed virus
preparation

Virus infection

Preculture
High density
culture
Virus propagation

Filling Centrifugation DNA removal

The vaccine is filled into
a vial or syringe
All components of the
final vaccine are Whole virus Virus inactivation
combined uniformly

Split vaccine
Formulation Polishing
Virus disruption

Subunit vaccine

Manufacturing mRNA vaccines

The mRNA is then

Genome
sequencing
AATGCGCTA
The sequence corresponding
to the mRNA is inserted into a
3 purified through
methods such as
Target CGCTACGAT chromatography to
pathogen CGACTCGAT plasmid within a cell. The
CAGCTAGCA plasmid is placed in a remove enzymes,
TTCGATCGA
reactor where enzymatic remaining nucleotides
reactions trigger the and defective mRNA.
synthesis of the mRNA.

1 2
The mRNA encoding
a specific antigen of the
infectious pathogen is
created from a DNA
template. This DNA
sequence can be shared
globally computer 4
systems in an instant.
mRNA delivery: As mRNA is
unstable, scientists are working on
various methods to encapsulate it
for delivery into the body.

Examples of delivery methods being explored are:3

Lipid-based Polymer-based Peptide-based Virus-like Cationic Naked mRNAs Dendritic cell-based

delivery delivery delivery replicon particle nanoemulsion mRNA vaccines

Challenges in vaccine development and manufacturing

Due to the inherent variability, development and manufacturing of a vaccine is exceptionally challenging. Here is an
overview of the key challenges at the global scale:

Viral mutations: As
seen with the
SARS-CoV-2 virus,
Vaccine development pathogens can
is an expensive mutate and new
process – if a strains evolve,
candidate fails it can which can mean
have huge financial redevelopment of
repercussions. already distributed
vaccines.

Manufacturing
requires highly
Failure in supply chains of skilled and
essential resources such as trained
culture media, filtration personnel.
equipment or vials can stall
manufacturing.

Knowledge on infectious
exposures of the intended
Vaccines are vaccine recipients required.
harder to
standardize
compared to
other biologics.

Low success rate Require large clinical

of early-phase trials to evaluate
development. immunogenicity and
safety in humans.

Challenges in vaccine distribution

There are also challenges specific to the distribution of a vaccine. In the case of the COVID-19 global pandemic, the
key difficulties that have been encountered include:

Communication
Racial and ethnic and trust
disparities

Funding
Federal, state,
Coverage and local roles
Supply and and costs
logistics

Future perspectives

The COVID-19 global pandemic has demonstrated that it is possible to manufacture and distribute a vaccine at
unprecedented speeds. Lessons learnt from this experience include the flexibility of mRNA vaccine platforms and the
value of single-use technologies that enable fast repurposing of manufacturing facilities. Continuous investment in

Tools strategies expertise

that enable the expansion of manufacturing capabilities will be essential in the future of
vaccine development and manufacturing.

Sponsored by

References:
1. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261-279. doi: 10.1038/nrd.2017.243.
2. Gomez PL, Robinson JM. Vaccine Manufacturing. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM, eds. Plotkin’s Vaccines. 7 ed. Elsevier; 2018:51-60.e1. doi: 10.1016/B978-0-323-35761-6.00005-5.
3. Verbeke R, Lentacker I, De Smedt SC, Dewitte H. Three decades of messenger RNA vaccine development. Nano Today. 2019;28:100766. doi: 10.1016/j.nantod.2019.100766.