I am a Clinical Immunologist, Immunopathologist, clinical researcher and laboratory scientist exploring the interactions between T cell and viral infections. My area of particular interest is the mechanisms by which HIV infection subverts effective T cel
Development Of Chimeric Hepatitis B Virus Like Particles As A Vaccine Delivery Platform For Multiple HIV-1 Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$139,500.00
Summary
The small envelope protein of hepatitis B virus (HBsAg) can self-assemble into highly organised viruslike particles with about 150 HBsAg-proteins forming a virus-like particle (VLP). VLPs induce an effective immune response, mainly against the exposed major antigenic site, the hydrophilic ‘a’- determinant region. To create a novel HBsAg-specific vaccine vector, foreign epitopes were inserted into the major antigenic site allowing surface orientation of the inserted sequence. Pilot studies involv ....The small envelope protein of hepatitis B virus (HBsAg) can self-assemble into highly organised viruslike particles with about 150 HBsAg-proteins forming a virus-like particle (VLP). VLPs induce an effective immune response, mainly against the exposed major antigenic site, the hydrophilic ‘a’- determinant region. To create a novel HBsAg-specific vaccine vector, foreign epitopes were inserted into the major antigenic site allowing surface orientation of the inserted sequence. Pilot studies involving the vaccination of mice with VLPs containing an epitope derived from the AIDS-virus (human immunodeficiency virus 1, HIV-1) or various hepatitis C virus-specific epitopes resulted in high titre antibody responses. This project aims for the development of a multi-component vaccine targeting a non-structural HIV-1 protein and therefore, avoiding the selective pressure directed against the structural proteins. The non-structural HIV-1 tat-protein is a multi-functional protein with an extracellular mode to sensitise uninfected cells for HIV-1 infection and to reactivate HIV-1 from quiescently infected cells. The use of eight tat-sequences is sufficient to provide coverage against 99% of HIV-1 sequences. We will develop hybrid particles that are composed of different sets of chimeric HBsAg proteins each containing a distinct tat-epitope. With this application, we aim to develop hybrid particles for the delivery of the complete set of tat-epitopes. The hybrid particles will be used for vaccination studies in mice, and the antibodies assessed by an in-vitro assay. This will lead to the development of a therapeutic and-or prophylactic HIV-1 vaccine, which could be used either for mass immunisation or in support of combination drug therapy and would have all the cost and production advantages of the widely used hepatitis B vaccine.Read moreRead less
I am an infectious diseases physician and basic scientist interested in the immunopathogenesis of HIV and hepatitis B virus. My work focuses on HIV viral reservoirs and immune reconstitution and the adaptive immune response to hepatitis B virus.
I am a medical epidemiologist investigating links between specific infectious agents and specific types of cancer in immune deficient populations. Through the exploration of these relationships, my research aims to allow the prevention of these types of c
Dissecting Mechanisms Of Generalised Immune Activation And Cellular Dysfunction In HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$422,576.00
Summary
How HIV infection compromises the host immune system is still not well understood. We will study how HIV surface proteins contribute to heightened immune activation during chronic infection. This generalised activation eventually leads to dysfunctional cellular immune responses and loss of partial control of infection. We will additionally investigate the extent and impact of the loss of functional immune responses in chronic HIV infection.
The Role Of Vif In Enhancing HIV Replication And Effecting The Integrity Of The Replication Complexes Of HIV
Funder
National Health and Medical Research Council
Funding Amount
$260,200.00
Summary
HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral l ....HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral life cycle. We aim to investigate the action of Vif in stabilizing early HIV reverse transcription complexes to understand how it acts to enhance HIV replication and viral infection. The early stages of HIV replication are critical for establishing infection and hence ideal targets for therapeutic intervention. This research will help understand how Vif works in a cell and affects the infectivity of HIV viral particles and may be suggestive of potential targets for development of anti-viral drugs.Read moreRead less
Escape And Reversion Of Critical Immune Responses: Insights Into Effective Immunity To HIV
Funder
National Health and Medical Research Council
Funding Amount
$372,446.00
Summary
The HIV pandemic is a global emergency. The overall goal of this grant proposal is to elucidate the requirements for protective immunity to HIV. Although immune responses have some effect on HIV replication, the virus mutates and evolves to escape immune pressure. However, each mutation away from wild-type virus likely results in at least some impairment in the ability of the virus to replicate. Where efficient immune responses target regions of the virus that are critical to virus replication, ....The HIV pandemic is a global emergency. The overall goal of this grant proposal is to elucidate the requirements for protective immunity to HIV. Although immune responses have some effect on HIV replication, the virus mutates and evolves to escape immune pressure. However, each mutation away from wild-type virus likely results in at least some impairment in the ability of the virus to replicate. Where efficient immune responses target regions of the virus that are critical to virus replication, escape mutations may result in viral variants incapable of causing disease. Resulting from an exciting collaboration between HIV and theoretical biologists, we have recently identified techniques to calculate the effectiveness of immunity and the cost of subsequent immune escape variants. We will use and expand these techniques to identify immune responses that result in the most effective control of viral replication. These studies will lead to ways to improve HIV vaccines and thereby prevent HIV.Read moreRead less