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New Generation Vaccines

Article in Expert Review of Vaccines · January 2014

DOI: 10.1586/erv.10.54

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New Generation Vaccines
Expert Rev. Vaccines 9(6), 551–553 (2010)
Expert Review of Vaccines Downloaded from informahealthcare.com by 188.134.76.66 on 05/20/14
Editor: Myron M Levine
For personal use only.
Publisher: Informa Healthcare, NY, USA
ISBN: 9781420060737, 1420060732
Vasso Apostolopoulos
Immunology and Vaccine Laboratory, Centre for
Immunology, Burnet Institute, 85 Commercial Road,
Melbourne, VIC 3004, Australia
Tel.: +61 392 822 111
Fax. +61 392 822 100
vasso@burnet.edu.au
www.expert-reviews.com
“The book ‘New Generation Vaccines’, by a distinguished editor
and associate editors, is a timely book in this important era in
the development of new-generation vaccines.”
Early vaccine studies
Initial vaccine attempts to prevent infec-
tious diseases were in 1000 AD in China,
whereby the contents of smallpox vesicles
were used to inject healthy individuals
who were subsequently protected against
smallpox. In the late 1790s, Edward Jenner
immunized an 8-year-old boy with cowpox
and then challenged him with smallpox;
the boy was found to be immunized against
smallpox. Thus, cross-reactivity from one
species of smallpox to another species of
smallpox resulted in protective immunity.
During the 19th Century, smallpox vac-
cination became increasingly popular and
eradication was accomplished in the dec-
ade of 1967–1977. In the last quarter of the
19th Century, Louis Pasteur noted that by
attenuating a pathogen from cholera, it was
possible to administer the attenuated strain
as a vaccine. The first attenuated bacterial
vaccine used in humans in 1884 was against
cholera. Although the vaccine was given to
approximately 30,000 individuals, most
of whom were protected, severe side effects
occurred and its use was halted. Pasteur and
colleagues also worked with viruses, espe-
cially rabies. They noted that if the spinal
cords were dried for 2 weeks, they lost their
ability to induce rabies. An immunization
schedule was set up with 42  dogs and,
although the results were extra­ordinary,
the vaccination procedure was quite con-
troversial in that deaths occurred in some
animals. Another approach was to use
killed viruses as a vaccine, such as the polio­
myelitis vaccine (Salk), which involved
treating the virus with formalin. This vac-
cine had a big impact on the incidence of
the disease prior to it being replaced by
10.1586/ERV.10.54 © 2010 Expert Reviews Ltd
Book Review
the live-attenuated version developed by
Sabin. The Sabin vaccine was inexpensive
and reliable whereas the Salk (dead) vaccine
was difficult to produce with inadequate
quality. Inactivated (dead) vaccines, which
are easy to produce at higher potency, are
now available but are impractical at a global
scale, even though they may be more effec-
tive than live­-attenuated vaccines. Measles
and poliomyelitis vaccines have now been
administered to infants and children as
live-attenuated vaccines.
Disasters
Despite the progress in developing vaccines
to a majority of diseases with protection
being noted, there were a number of dis-
asters in humans; in 1932, the Lubeck
disaster for the bacillus Calmette–Guérin
vaccine, the Bundaberg tragedy in 1928 for
the diphtheria vaccine, and the Cutter dis-
aster in 1955 for the Salk-type vaccine. All
these disasters were due to improper labo-
ratory manufacturing and handling and,
consequently, these cases led to improved
procedures for the safety of vaccines, and
led to regulatory measures to assure proper
laboratory conditions, training of person-
nel and improved procedures in laborato-
ries where vaccines were manufactured.
With attempts to control more complex
diseases, and the need to improve vaccine
safety, stability, efficacy and cost, there
is pressure for more and more precisely
defined vaccines.
Development of safer & more
effective vaccines
Public awareness of occupational health
and safety issues is now much higher
ISSN 1476-0584 551
 Book Review Apostolopoulos
than it was 50 or more years ago. Vaccines must now meet
higher standards of safety and biochemical characterization
than they did in the past. Some of the vaccines developed in
the past would not even meet the minimum standards required
today. Thus, for a vaccine regime to be successful today, one
needs to use new molecular and biological techniques that have
been developed in the last 10 years – these techniques are use-
ful in the generation of new and improved vaccines. Advances
in the fields of molecular biology, chemistry and immunology
are now used in the development of new and improved vac-
cines, in an attempt to move from traditional live viral and
bacterial vaccines to the theoretically ‘safer’ but ‘less immuno-
genic’ vaccines. The application of genetic and recombinant
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DNA approaches, protein production techniques and synthetic
peptide chemistry has led to new and safer vaccines; however,
there are still many obstacles for their clinical use. The limited
immunogenicity of many of these candidates has hindered their
development as potential vaccines for humans. Strategies to
enhance the immunogenicity of candidate vaccines have had
to be developed.
Approaches to enhancing immunogenicity
Adjuvants have been developed that, when mixed with proteins,
peptides or DNA, could amplify either or both the humoral
For personal use only.
and cell-mediated immune responses to that antigen. The most
frequently used adjuvant in experimental animals is complete
Freund’s adjuvant. Although very effective in evoking an effec-
tive and long-lasting immune response, complete Freund’s adju-
vant is not suitable for human use because it induces granulomas,
fever and inflammation due to the oil and myco­bacteria. There
is only one registered human adjuvant (aluminium hydroxide or
aluminium phosphate) which is used in the diphtheria, tetanus
and hepatitis B vaccines. Aluminium salt adjuvants are limited
in their use in that they preclude lyophilization or freezing, they
are not effective with all antigens and they do not stimulate
cell-mediated immunity. Candidates for alternative adjuvants
for vaccine development include: the Syntex formulation, SAF-1
(containing squalene oil, an amino acid derivative of muramyl
dipeptide [threonyl-MDP] and nonionic block polymers); the
Ribi formulation (containing myco­b acterial cell walls and
monophosphoryl lipid A); and the saponin derivative, QS21
(also called Quil A). The development of new adjuvants, how-
ever, has been dominated by concerns about safety, since most
of the adjuvants that have been developed to date are too toxic
for use in humans. More recently, liposomes (phospholipid-
based vesicles) have been used to deliver antigens, in addition
to the incorporation of antigens into solid particles such as
immunostimulatory complexes. Other approaches for vaccine
development include viral vectors, use of nanoparticles, tar-
geting antigens to receptors on dendritic cells and the use of
Toll-like receptor ligands to enhance immunity to the antigen.
The future holds promise for new vaccines to prevent, con-
trol and possibly eradicate diseases, including cancer. All the
techniques described should lead to the production of new and
effective vaccines.
552
New-generation vaccines
The book ‘New Generation Vaccines’, by a distinguished editor
and associate editors, is a timely book in this important era in
the development of new-generation vaccines. The book includes
89  up-to-date chapters in the development of vaccines. The
chapters are clear and informative, with key tables and figures.
The book begins with a chapter on historical perspectives and
immediately enters into modern methods of defining vaccine
antigens by reverse vaccinology. Initial clinical trials are evalu-
ated, issues required for vaccine trials in developing countries
are addressed, clinical trials into Phase III and IV are evaluated,
ethical considerations are discussed, the economics of clinical
trials are mentioned, an industry perspective is given on the
development of vaccines, and achieving global immunization
is discussed. The paradigm of global alliance for vaccines and
immunization is nicely presented, followed by an economic
analysis of vaccine programs, US FDA licensing of vaccines,
vaccine safety and manufacturing, and the work of the WHO is
analyzed. Efforts into the eradication of polio are discussed and
recent immunological advances that impact vaccine development
are assessed.
“...for a vaccine regime to be successful today, one
needs to use new molecular and biological
techniques that have been developed in the last
10 years – these techniques are useful in the
generation of new and improved vaccines.”
This is followed by 23 chapters discussing the modulation of
innate immunity, immunodominance of antigens, measurement
of T-cell responses, assessment of multivalent vaccines, vaccina-
tion and developing autoimmunity, adjuvants, Toll-like receptor
agonists for enhanced immune responses, mucosal vaccines, nan-
oparticles, lipopeptide vaccines, use of dendritic cells to deliver
vaccines, viral vectors, DNA vaccines, prime–boost approaches
and transcutaneous vaccine delivery systems.
The next 44 chapters discuss specific vaccines developed for
numerous diseases of bacterial and viral origin. These include
vaccines against meningococcus, influenza, Salmonella, cholera,
TB, dengue, rotavirus, measles, HIV, hepatitis C, respiratory
syncitial virus, cytomegalovirus, Epstein–Barr virus, herpes
simplex, rheumatic fever, Streptococcus, Shigella, Escherichia coli,
Staphylococcus aureus, Chlamydia trachomatis, malaria, Leish­
mania, schistosomiasis, Entamoeb histolytica, hookwom, small-
pox, anthrax, tularemia, plague, Ebola and Marburg viruses, lassa
fever, hantavirus and SARS.
The final five chapters touch on the development of cancer
vaccines, including the approved vaccine against cervical can-
cer, vaccine development against Alzheimer’s and other neuro­
degenerative diseases, and against autoimmune and chronic
inflammatory disorders. The final chapter discusses an interesting
topic in the use of vaccines to treat drug addiction.
Overall, the book addresses a range of important issues in
the development of new-generation vaccines. It provides a solid
overview of vaccine development and is greatly useful to a range
Expert Rev. Vaccines 9(6), (2010)

of target audiences, such as immunologists, molecular biologists,
chemists and investors in pharmaceutical companies who are
interested in the development of new-generation vaccines.
Financial & competing interests disclosure
Vasso Apostolopoulos would like to thank the Susan G Komen for Cure Breast
Cancer Foundation (USA), Bosom Buddies Breast Cancer Foundation
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New Generation Vaccines Book Review
(Australia), and the Beauties and the Beast (Australia) for providing funding
directly to her laboratory for the development of breast cancer vaccines. The
author has no other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript apart from
those disclosed.
No writing assistance was utilized in the production of this manuscript.
553