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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).
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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. One approach we have used is to genetically engineer vaccines to encode their own cytokine genes or co stimulatory molecules to analyse their function in vivo and determine whether enhanced immune responses are induced. We are also using the cytokine genes to modify the pathogenicity of viruses which may now enable us to engineer safe live-vaccines. We are also combining our co expression approach to study the role of toll-like receptors (TLR) in viral infection. TLR’s are primary immune sensors that regulate cytokine expression in host antiviral defense. Mice lacking TLR’s are more highly susceptible to virus infection however this can be overcome by providing interferon-b through the viral encoded co expression technology indicating the critical antiviral role of this cytokine. This approach is also being used to study other cytokines. |
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Molecular Mucosal Immunology Laboratory.
Leader: Dr. Charani Ranasinghe
Since all HIV-1 “systemic vaccine trials” in humans have
elicited poor outcomes, there is now an increased awareness of the
potential importance of inducing local antiviral immune responses
at “mucosal surfaces”, particularly in the genital and
rectal tissues, the cervico-vaginal tissues in females where the virus
is usually first encountered, and in the gastro-intestinal tract,
which appears to be a major site of virus replication. It is now widely
accepted that, purely systemic immunisation strategies for example;
intramuscular, intravenous although inducing good systemic T cell
responses rarely induce optimal sustained mucosal T or B cell immunity.
It has been shown that a direct mucosal application of a vaccine is
necessary to induce sustained mucosal immunity. Furthermore, we have
shown that the mucosal vaccination can induce better quality CD8+
T cells (T cells of higher avidity) compared to systemic vaccination.
Therefore, in our laboratory we are currently evaluating the efficacy
of new-generation of pox virus HIV vaccines that could be delivered
intra nasally, orally, and/or systemically, that could enhance the
magnitude, cytokine profile as well as the avidity of both mucosal
and systemic CD8+ T cells. Several immunological and molecular techniques
such as ELISpot, intracellular cytokine staining, tetramer staining
and PCR based assays have been developed in our laboratory to assess
the immune responses to vaccine antigens.
Our laboratory is mainly focused on
1. Evaluating the quality of HIV specific mucosal and systemic T cells
generated by prime boost vaccination. In order to achieve this, profiling
of mucosal and systemic T cells are being performed in the laboratory.
2. Understanding the molecular mechanisms governing the induction
of high avidity CD8+ T cells following mucosal prime boost vaccination.
3. Identifying novel molecules (i.e. cytokines, chemokines) that could
be utilised as molecular markers to measure mucosal immune responses
to vaccine antigens.
4. Identifying novel molecular adjuvants to enhance mucosal immune
responses to vaccine antigens. |
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