Mucosal Human Immunodeficiency Virus Vaccine Late Pre-clinical Evaluation
Funder
National Health and Medical Research Council
Funding Amount
$575,315.00
Summary
Despite many candidate vaccines entering clinical development for protection against HIV, none has yet been successful. This proposal centres on late preclinical development for a novel mucosal vaccine strategy for HIV, which combines a preclinically-proven approach to generating strong T cell immune responses, with an existing approach to generating broadly neutralising antibody responses to HIV. Proof of synergy between these approaches will lead directly to clinical development.
Immune Modulatory Effects Of Vaginal Microbiota Metabolites And HIV Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$795,110.00
Summary
This study will advance knowledge on how acid molecules produced by beneficial and harmful bacteria are able to promote or impede HIV infection of the female genital mucosa through their effects on the barrier and immune function of cells that line the vagina and cervix. The results of this study are anticipated to augment the efficacy of topical HIV prevention strategies and lead to the development of safe vaginal hygiene products that help protect against other sexually transmitted infections.
I am an infectious diseases physician and virologist/immunologist focused on developing and testing vaccines against the AIDS virus. I intend to achieve this by advancing novel vaccine concepts that stimulate broad and potent immunity and evaluating these vaccines in rigorous laboratory models and then moving them towards clinical trials.
The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.
A vaccine for hepatitis C virus (HCV) is not yet available. Immune responses that are able to protect against infection are possible, making the production of a vaccine a realistic goal. We have produced a unique HCV vaccine and are now poised to test our vaccine in novel humanised animal models. Our research will allow us to determine the immune responses responsible for providing protection against HCV. Our data will be highly significant for future HCV vaccine studies in humans.
Understanding The Role Of NS Segments In Evading Influenza A Virus-specific Humoral And T Cell Immunity
Funder
National Health and Medical Research Council
Funding Amount
$213,812.00
Summary
Influenza viruses developed two ways to survive against host immune response: (i) mutating in its genes to escape host immune response, which may cause a new pandemic; (ii) using its NS1 protein to impair host immune response. However, little is known on how these two processes occur and whether NS1 could influence the outcome of escape mutants. By using virological and immunological methods, this study will show how viruses use different NS1 to enhance the viral escape mechanism.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
We will construct different genetically engineered viruses, which infect cells in the respiratory tract, to deliver genes encoding proteins from human immunodeficiency virus (the AIDS virus). These engineered viruses can be expected to generate an active immune response in mucosal tissues, including the vaginal and rectal tracts. As these are the major routes for transmission of the AIDS virus, these new vaccines are expected to reduce transmission of the AIDS virus.
What happens when viruses infect cells? How do they control the cells they infect? How do the make the cells do the things the virus wants? These are the questions that we aim to address within this research proposal. Primarily we hope to identify how viruses are able to replicate in cells and avoid immune detection. We believe these processes are related.
Understanding And Modulating Hyperinflammation Caused By Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
In humans, highly pathogenic influenza A virus (IAV) infections can be fatal, as the disease is untreatable with available vaccine or anti-viral drugs. My fellowship aims to advance our knowledge of the mechanisms by which the immune system induces and regulates inflammation during IAV infection, which can be both helpful and detrimental in fighting the infection. This is critical for identifying and developing new therapies for severe IAV infections in the future.