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Research
Our Group has been responsible for construction and testing of the
DNA component of this vaccine. This is the largest grant yet given to
an Australian research team from an international agency. Several significant
obstacles remain, however, for eventual wide scale application of these
approaches in humans. Importantly, since the HIV epidemic is global,
and the different isolates of HIV differ significantly in sequence homology,
an effective vaccine must be able to protect a genetically diverse human
population against a wide range of viral isolates. We are currently
developing the next generation of HIV vaccines to address this issue
(see details below).
Immune Regulation and Vaccine Development Laboratory
Leader: Professor Ian Ramshaw
The focus of our research is to study the factors important in
generating high levels of protective immunity to vaccination.
In particular, we are concentrating on the use of prime boost
immunisation to stimulate high levels of cell-mediated immunity.
We have been studying why this vaccination strategy generates
such a powerful response. Using a tetramer staining technique
we have been able to show that DNA vaccines are able to induce
very effective or high avidity T cells which are then expanded
by boosting with a recombinant fowlpoxvirus vaccine encoding the
same vaccine antigen. The quality of an immune response generated
by a particular vaccine strategy may therefore be as important
as the levels of immunity induced. Vaccines that generate T cell
populations of high avidity, optimising the early detection of
infected cells, offer new hope for development of effective prophylaxis
against pathogens such as HIV, which have presented major problems
for vaccine development. |
Molecular Mucosal Immunology Laboratory
Leader: Dr. Charani Ranasinghe
Developing vaccines that generate immune responses at the initial viral
entry site, (i.e. mucosal surfaces such as cervico-vaginal tissue, rectal
tissue) is thought to be important in controlling diseases such as HIV.
It has been shown that a direct mucosal application of a vaccine is
necessary to induce high-quality mucosal immune responses in animals.
Currently, we are evaluating the use of recombinant “Pox virus”
prime boost vaccine strategies (recombinant HIV-FPV/ recombinant HIV-vaccinia
virus) to induce HIV specific mucosal and systemic immune responses
to vaccine antigens. In order to assess the vaccine routes that generate
both mucosal and systemic immune responses a range of mucosal and/or
systemic vaccine delivery routes are being tested in the laboratory.
Effect of co-expression of stimulatory molecules such as cytokines to
enhance the immune responses is also being evaluated. Several immunological
and molecular techniques such as ELISPOT assays (IFNg, TNFa IL.2, IL.4),
intracellular staining of cytokines, tetramer staining and real time
PCR based assays have been developed in the laboratory to assess the
immune responses to HIV vaccine antigens.
Our laboratory is also focused on evaluating the quality of HIV specific
mucosal memory T cells generated by these vaccines. In order to achieve
this, profiling of mucosal memory T cells is currently being performed
in the laboratory. Further more, the group is also interested in characterising
the molecular mechanisms governing the mucosal prime boost vaccines
with a view to identifying novel molecules or cytokines that could be
utilized as a) molecular markers to measure mucosal immune responses
to vaccine antigens and/or b) molecular adjuvants to enhance mucosal
immune responses to vaccine antigens.
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