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| Mission Statement |
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| The Vaccine Development laboratories at
IVI are dedicated to developing new, or adapting
existing, vaccine manufacturing processes,
for the purpose of providing such technologies
to vaccine manufacturers in developing countries.
The goal of these technology transfers
is to provide vaccines to the most needy
at affordable prices, thus contributing
to reducing the burden of disease in developing
countries.
Our prime focus is on developing or acquiring
vaccine technologies for the prevention
of diseases that afflict the world's poorest
people but are generally very low incidence
in wealthier countries. Consequently these
vaccines are of only minor interest to the
large multinational vaccine manufacturers
where the costs of development could not
be justified by the financial returns.
Currently our main interest is in vaccines
for prevention of Typhoid fever, Shigellosis
and Cholera. The projects are briefly described
in the following pages:
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| Shigella Vaccine Development |
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| There are over 160 million episodes of shigellosis
annually and estimates of annual mortality
are as high as 1 million, the vast majority
occurring in developing countries. Outside
of China there are no licensed vaccines for
the prevention of Shigella infection. Several
strategies to develop a vaccine have been
applied. Live attenuated bacteria have been
developed as candidate vaccines but it has
been difficult to find the right balance between
attenuation and immunogenicity, the more immunogenic
mutants tend to produce symptoms of disease
whereas less attenuated strains are poorly
immunogenic. Conjugate vaccines have shown
promise but a vaccine containing a minimum
of five specific O antigens (detoxified polysaccharide
from Lipopolysaccharide (LPS)) conjugated
to a protein carrier may prove to be too expensive
for routine vaccination. |
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| At IVI we are developing a vaccine for the
prevention of Shigellosis based on the discovery
that ribosomes from the Shigella bacteria
have specific O antigen non-covalently bound
to their surface. The O antigen on the ribosome
is free of the lipid A associated with O antigen
in LPS. Previous attempts to purify the ribosomes
from Shigella yielded material contaminated
with LPS resulting in the preparations containing
unacceptable levels of endotoxin. We have
developed a novel method for the removal of
the LPS from the ribosome fraction so now
have a realistic vaccine candidate. Preliminary
results in mice have shown good antibody responses
both in serum and feces following parenteral
injection with the purified ribosomes. Pre-clinical
work will continue with the eventual aim of
producing GMP lots at a selected developing
country vaccine manufacturer for the purpose
of conducting clinical trials and eventual
licensing of the product. |
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| Conjugate Vaccine Development |
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| The Conjugate Vaccine Section (CVS) of Vaccine
Development Department at the IVI is dedicated
to advancing candidate glyco-protein conjugate
vaccines from the laboratory to the clinic,
with the particular emphasis on techniques
suitable for eventual large-scale manufacture
of conjugate vaccines. We plan to develop
Vi conjugate vaccine with the assistance of
National Institutes of Health, U.S.A., as
our first project. The technology will then
be transferred to vaccine manufactures in
developing countries. We will develop appropriate
quality control and release tests, pre-clinical
testing of the vaccine, and assist with the
scale up of the manufacturing process. Through
partnership with vaccine manufacturers in
developing countries we will assist in providing
clinical grade material for Phase I/II and
Phase III clinical trials with the eventual
aim of introducing the vaccine into these
countries. |
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| Technology Transfer |
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| Introduction and routine use of a vaccine
in developing countries requires a reliable
supply of vaccine at a relatively low price.
The large multinational vaccine manufacturers
can not be relied upon to supply low cost
vaccines to meet the specific requirements
for health care in developing countries. To
guarantee supply of vaccine at an affordable
price it makes sense to have regional vaccine
manufacturers that are capable of producing
vaccine to acceptable quality standards. It
can be difficult for these manufacturers to
gain access to certified seed strains as well
as vaccine manufacturing and testing technologies.
Many attempts to transfer vaccine technologies
have been unsuccessful for various reasons
including lack of proper documentation including
Standard Operating Procedures for production
and testing of the vaccine. More importantly
these technology transfers did not include
proper training and support for the company
taking up the technology. It is our intention
when transferring technology that IVI provide
the recipient with complete documentation
and thorough training in manufacturing and
quality control. In addition the National
Regulatory Authority will be trained in
lot release assays.
IVI is working with a Vietnamese vaccine
manufacturer of Oral Whole Cell Cholera
vaccine to ensure that the vaccine meets
the draft standard published by WHO for
this vaccine. IVI is also assisting with
the preparation of documentation in readiness
for the transfer of the vaccine technology
to an Indian vaccine producer and the eventual
licensing of the product in India.
In addition we are providing technical
assistance with Typhoid Vi vaccine manufacture
and testing to various developing country
vaccine producers.
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