Download Vaccine discovery and translation of new vaccine technology

Andrew A. Potter and Volker Gerdts, VIDO-InterVac, Saskatoon, SK
Feature
Vaccine discovery and
translation of new vaccine technology
I
nfectious diseases have historically
been the leading cause of morbidity
and mortality world wide, a situation
that has not changed significantly to
this day. Approximately one quarter (¼) to
one third (1⁄3) of all deaths are due to infectious diseases and although emerging
diseases such as pandemic Influenza, West
Nile virus, etc. have been in the public eye,
persisting infections such as tuberculosis
and seasonal influenza continue to have a
profound effect in all countries with greater
than two million deaths each year.
However, there will be a number of challenges which need to be addressed if we
are to realize the full potential of vaccines
and vaccination programs.
Vaccine Discovery
We have seen a revolution over the
past 3 decades in the fields of molecular
biology, genomics, and immunology; tools
which have all been applied to vaccine
development. For example, it is possible
to develop vaccines without the ability to
culture a pathogen in pure form through
Canada has been a key player in the development of new vaccine technologies over the past 50 years with key contributions
to polio and pertussis vaccine development as well as the development of conjugate vaccines for others, such as meningococcal
infection.
During the past century, vaccines have
proven to be the most effective tool for
the control of infectious disease. While
only one human disease, Smallpox, has
been eradicated through immunization,
there is no question that numerous others have been successfully controlled on a
global scale, including polio. Canada has
been a key player in the development of
new vaccine technologies over the past 50
years with key contributions to polio and
pertussis vaccine development as well as
the development of conjugate vaccines for
others, such as meningococcal infection.
Indeed, the contribution of Connaught
Laboratories (now Sanofi Pasteur) to the
growth of polio virus was truly an enabling technology. Canada’s contribution
to the global vaccinology field has been
enabled by strong support for infrastructure, people, and resources over the past
decades resulting in a cadre of personnel
who carry out truly innovative research.
Volume 19/Issue 2 Summer 2012
the process of “reverse vaccinology”. This
involves the identification of potential
vaccine antigens in silico (reviewed by Vivona et al, 2008), usually surface-exposed
proteins, ranking them based on a variety
of factors and finally testing their vaccine
potential in animal disease models. This
approach was pioneered by Rino Rappuoli and colleagues at Novartis for meningococcal vaccine development (Pizza
et al, 2000) and has since been applied to
numerous other diseases, primarily those
caused by bacterial infection. Other types
of new vaccines that are conceptually similar include nucleic acid (DNA or RNA)
products. These contain a gene coding for
a protective antigen as well as sequences
for expression in a mammalian host, thus
turning the immunized person into a bioreactor. This type of vaccine has been
tested in clinical trials for over a decade
and products are just starting to see use in
areas such as Cancer vaccines as well as
in combination with other vaccine types.
In the case of live vaccines, considerable
discovery research has been conducted
on novel methods for reducing virulence,
or attenuation, as well as the construction
of live vectored vaccines which protect
against the carrier organism as well as
other infectious agents.
Vaccine Formulation
and Delivery
While we have seen phenomenal advances in the identification of potential immunogens, the way vaccines are formulated and delivered remains an area which will
define future increases in efficacy. Indeed,
the majority of killed vaccines are injectable products which are formulated with
Alum as an adjuvant, thus limiting their effectiveness due to the quality and quantity
of immune responses which are induced
following immunization. An excellent example of this is the case of acellular Pertussis vaccines, currently formulated with
Alum, which require >5 immunizations.
While this vaccine is a major step forward
relative to the whole cell Pertussis vaccines previously used, the requirement for
this many booster immunizations is well
beyond the capabilities of many healthcare systems to deliver, including parts of
Canada. Thus, reformulation of this and
other vaccines with adjuvants capable of
inducing balanced, long-lasting immunity,
is critical in our view. In addition to the
formulation, the route of immunization
needs to be re-examined; the induction of
immunity at mucosal surfaces such as the
respiratory tract is best achieved by mucosal immunization. Figure 1 illustrates both
of the above points for an experimental
Pertussis vaccine which was formulated
with a novel adjuvant and delivered via
the intranasal route. In this case, a single
vaccine dose to either mice or pigs during
Continued on page 6
5
Feature
Continued from page 5
The Future
There are a variety of persisting, emerging, and new disease targets for vaccine
development, including global priorities
such as HIV, malaria, and tuberculosis. The
newer approaches to vaccine formulation
and delivery described above, as well as
others, have provided exciting new clinical
results for these pathogens and we expect
the first week of life resulted in protective
immunity lasting over 2 years. The ability
of vaccines to induce balanced immunity
is critical for protection against the diversity of strains circulating in the population,
a problem currently being experience in
Australia.
Figure 1
Immune responses following immunization
of mice with Pertussis toxoid formulations
1,000,000
Titre
100,000
■
■
■
■
■
Triple adjuvant
■
■
10,000
100
PTd + alum
■
1,000
●
✴
■
2
4
✴
●
●
✴
6
8
✴
✴
●
10
✴
●
✴
●
12
14
●
✴
✴
●
✴
16
PTd
19
Weeks Post Immunization
Mice were immunized with Pertussis toxoid (PTd) alone, PTd plus Alum or PTd formulation in a
new adjuvant composed of three components delivered intranasally. Antibody titres (IgG2A) were
measured every two weeks.
to see older products modified as well to
reduce the number of immunizations and to
target specific risk groups such as neonates
and the elderly. Over the next decade, we
can expect to see:
1. Efficacious vaccines for high priority
targets such as HIV, malaria, and TB.
2. Movement towards non- or minimallyinvasive routes of vaccine delivery.
3. New technologies which will provide
enhanced, broad-spectrum immunity
against infectious agents such as influenza.
4. New non-infectious disease vaccines
(cancer, behavior modification).
In order to accomplish this, Canada
must continue to invest in vaccine research
and development from the bench through
to the clinic and our regulatory system
must be overhauled to deal with the realities of the timely licensure of products for
Canadians. ❖
References:
1. Pizza, M., et al, 2000. Science 287,
1816-1820.
2. Vivona, S. et al, 2008. Trends Biotechnol 26, 190-200.
Hello
from the
OSMT staff
With the addition of a new
OSMT staff member, Carrie Kelly,
we decided to take a picture to reintroduce all of us at the office.
We’re enjoying renovated quarters
and invite our members to drop by
anytime to say hello.
❖
Pictured left to right: Debbie Brooks, Amy Yu, Blanca McArthur, Carrie Kelly, Margaret Faye
6
ADVOCATE