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This book was written during the Covid-19 pandemic. Globally, as of 24th
January 2022, the WHO estimates over five and a half million deaths from
the SARS-CoV-2 virus have been reported to the WHO. This worldwide
health crisis has highlighted the need for the rapid development of effective,
affordable vaccines that can be quickly deployed to all countries, especially
low- and middle-income countries (LMICs).
Healthcare companies and academic institutions across the world
answered this need with remarkable speed and ingenuity, with a plethora of
vaccine candidates (over 100) in clinical development during 2021, and a
handful already approved for mass immunization programs. Regulatory
authorities worked closely with those developing new vaccines to facilitate
approval processes, and activities that would normally be carried out sequen-
tially, for example, scaling up good manufacturing practice (GMP) manufac-
ture and different phases of clinical testing, were parallel tracked tracked to
reduce overall timelines.
The majority of Covid vaccines target the SARS-CoV-2 surface Spike (S)
protein, which is an important target antigen for neutralizing antibodies.
A variety of approaches for subunit vaccines have been applied, including
RNA, DNA, viral vectors, protein in adjuvant, and virus-like particles (VLP).
The more traditional “whole cell” approach has also been used, with both
inactivated and live-attenuated viral vaccines.
In the 21st century, outbreaks of several viruses including Ebola, MERS
(Middle East respiratory syndrome), SARS (severe acute respiratory syn-
drome), influenza, Zika, and Chikungunya have affected numerous countries
worldwide. Many researchers are aiming for a platform technology approach,
with a single vaccine design (e.g., viral vector or RNA formulated in lipo-
somes), which can be rapidly adapted to create vaccines against emerging
pathogens or new pathogen strains.
It is clear that several challenges remain in the rapid international deploy-
ment of effective vaccines. These include the required scale-up in GMP man-
ufacture of new vaccines to produce the billions of doses required in a
pandemic situation. Manufacturing capacity is rate limiting, especially in
LMICs that lack the expensive facilities required for production of vaccines
and other biological medicines. It is also challenging to deploy vaccines
internationally, especially those that need to be stored at low temperatures,
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as many regions of the world lack freezer equipment and electricity supply
cannot be guaranteed.
This book is a collaboration between scientists based in several different
countries including Nigeria and the UK, and is representative of the many
ongoing international collaborations in vaccine development, and more gen-
erally in the fight against infectious diseases. The editors intend the book to
be used by scientists who are developing new vaccines and teaching the con-
cepts of vaccinology to students.
Early chapters review the basic immunology that underpins the concept
of immunization and the varied approaches that have been taken to develop
vaccines. One chapter focuses on practical methods that can be implemented
in evaluating antigens as vaccine candidates, including immunomonitoring in
clinical trials. Later chapters explore recent developments in vaccine
research, including the use of immunopeptidomics to identify target T-cell
epitopes, and approaches to developing cancer vaccines, a rapidly expanding
area of research due to the discovery of tumor-specific neoepitopes that can
be targeted by an immune response while sparing normal tissue.
We have included a comprehensive review of adjuvants, which can
greatly improve the immune response to subunit vaccines, especially soluble
proteins and VLPs. Finally, there is a practical guide to the principles of
GMP manufacture and to the planning and execution of clinical trials.
As the Covid-19 pandemic has illustrated, vaccines can have a global
impact in controlling disease and saving lives. Ground-breaking science and
international, multidisciplinary collaboration are key in advancing vaccine
development. There remains much to be done, in preparing for future out-
breaks, and in developing more effective vaccines against diseases with high
mortality rates in certain areas of the world, for example, Ebola hemorrhagic
fever, malaria, HIV, and tuberculosis.
Manipulation of the immune system by vaccination
Daily, millions of people worldwide benefit from modulation of the immune
system via immunotherapy. Unfavorable immune responses can be controlled
to treat autoimmunity, allergy, and transplant rejection, and conversely
responses can be stimulated to treat cancer, or induce protective immune
responses against pathogens using vaccines. Immunization (also known as
vaccination) is the most widely practiced form of immunotherapy. It is rec-
ognized as perhaps the greatest triumph of modern medicine, attributed origi-
nally to Edward Jenner who was the first to use a scientific approach to
immunization in 1798. He utilized observations made about two decades ear-
lier by a farmer, Benjamin Jesty, that individuals exposed to cowpox were
protected against smallpox. The term vaccination originates from the Latin
word “vacca” for cow after Jenner successfully demonstrated that inoculation
with cowpox could protect against the often-fatal smallpox virus. It is inter-
esting to note that Jenner knew nothing of the infectious agents that cause
disease. Neither did he understand the basis for the consequent immunity
that resulted following his vaccination. Therefore, despite the huge success
of his vaccinations in offering protection against smallpox, findings from his
work remained unexploited for almost a century.
This narrative changed when Louis Pasteur, together with Camile Gue ́rin
and Albert Calmette, demonstrated that weakening a pathogen could stimu-
late protective immune responses against that specific pathogen without
causing disease. This is termed attenuation and was the basis for production
of the Bacille Calmette-Guerin (BCG) tuberculosis vaccine, which was first
used in 1921, and remains in use today. Pasteur made the germ theory of dis-
ease famous and also opined that vaccination could actually prevent infec-
tious diseases. For this reason, Louis Pasteur is considered to be the founder
of modern immunology. Robert Koch built on the work of Pasteur and was
able to prove that infectious diseases are caused by microorganisms. These
discoveries extended Jenner’s vaccination strategy to other diseases.
The essential strategy for vaccination is to prepare an innocuous form of
a pathogen, or individual pathogen antigens, that are immunogenic and can
establish memory cells and protective immunity. This can be achieved using
killed or live attenuated organisms, purified microbial components or recom-
binant antigens. In the case of Edward Jenner’s landmark experiment, cow-
pox was a closely related but much less dangerous pathogen that was able to
offer cross-protection against the virulent and dangerous smallpox.
Approaches to vaccine design are described in more detail in Chapter 2,
Vaccine Types and Reverse Vaccinology.
