HIV infection is a dynamic process, in which the host immune response tries to control viral growth and keep up with the rapid evolution of the virus. This project assembles an interdisciplinary team of mathematicians and biologists to use a modelling approach to understand the dynamics of viral infection, viral evolution, and immune control in the infected individual. The insights gained from this project will help in the development of new drug and vaccination strategies.
Pre-clinica Evaluation Of A Novel HIV-1 Vaccine Statrgy
Funder
National Health and Medical Research Council
Funding Amount
$528,440.00
Summary
Recently, we have designed two mucosal HIV vaccine strategies that temporary block hormone-like molecules IL-4/IL-13 at the vaccination site inducing excellent antibody and killer T cell immunity with protective efficacy in small animals. This project aims to evaluate the safety and efficacy of these novel HIV mucosal vaccines prior to clinical evaluation.
Understanding The Role Of Host Arih2 In Defence Against Viral Infection And Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,737.00
Summary
A set of proteins, called E3 ligases, modulate many aspects of immunity. Arih 2 is a novel E3 ligase that limits immune cell activation to maintain the immune system in a quiescent state. The details of how Arih2 functions and its role in immunity to chronic overwhelming infection are the focus of this study. The insights gained from these studies have important implications for our understanding of how immune responses can be promoted during infection or halted in autoimmunity.
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.