Molecular Basis Of T Cell Receptor Bias In Viral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Viral infection results in the activation and proliferation of T cells that eradicate infected cells. Recognition of infected cells is meditated by presentation and recognition of viral protein fragments via specific cell surface receptors. This proposal plans to examine the factors that determine the diversity of the immune response and the consequences of such diversity on anti-viral immunity. This has implications for the development of vaccines.
While current influenza vaccines blunt winter epidemics, they must be updated frequently to keep up with virus mutation and they do not protect against pandemics caused by new flu viruses (such as bird flu). This program will define how flu virus interacts with the immune system to generate immunity mediated particularly by “killer” T cells. We will use this knowledge to develop and evaluate vaccines that induce long-lasting T-cell immunity that can protect against both seasonal and pandemic flu ....While current influenza vaccines blunt winter epidemics, they must be updated frequently to keep up with virus mutation and they do not protect against pandemics caused by new flu viruses (such as bird flu). This program will define how flu virus interacts with the immune system to generate immunity mediated particularly by “killer” T cells. We will use this knowledge to develop and evaluate vaccines that induce long-lasting T-cell immunity that can protect against both seasonal and pandemic flu.Read moreRead less
Long-lived CD8 T Cell Responses Induced By A Recombinant Cytomegalovirus Vector
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
The priming of the immune system to protect against infection and disease is an important means to alleviate these conditions. Current vaccination technologies often rely on multiple inoculations (prime-boosting). In addition, specific priming of the immune system against pathogens that target mucosal sites has been difficult and often lacks efficacy resulting in temporary or variable protection. Using a well developed mouse model for a common human virus, we have explored the potential of this ....The priming of the immune system to protect against infection and disease is an important means to alleviate these conditions. Current vaccination technologies often rely on multiple inoculations (prime-boosting). In addition, specific priming of the immune system against pathogens that target mucosal sites has been difficult and often lacks efficacy resulting in temporary or variable protection. Using a well developed mouse model for a common human virus, we have explored the potential of this agent as a vaccine agent, making use of its long term persistence in the infected host to provide continued antigenic stimulation of the immune system. We have found that very strong and long lasting responses can be elicited after a single inoculation of avirulent virus. In this study, this effect will be further explored and developed.Read moreRead less
Cytolytic Mechanisms Required For Virus Elimination.
Funder
National Health and Medical Research Council
Funding Amount
$698,567.00
Summary
Viruses provoke devastating disease. The immune system kills cells that are infected with viruses. To do this, immune cells release granules that are packaged with different killer molecules. It is unknown which killer molecules participate over the course of an immune response to virus. Here, we will investigate this process for cells that are infected with influenza A virus and herpes simplex virus. This study will allow the design of strategies to limit widespread damage inflicted by viruses.
Interplay Of Innate And Adaptive Immunity To Influenza A Virus
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Influenza is an acute febrile respiratory illness caused by influenza virus infection, and may trigger potentially life-threatening complications especially in the young and elderly. Immunity against influenza virus involves integration of the innate and adaptive immune system. We will use cutting-edge 2-photon microscopy to determine the orchestration of innate and adaptive immune cell interactions during viral infection. Results may provide for enhanced therapeutic or protective measures.
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.
Tapasin And Major Histocompatibility Complex Class I Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. ....An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. This research proposal aims to examine the role of tapasin in this regard. A thorough understanding of the basic principles of peptide presentation to T cells is crucial to the design of effective vaccines. Furthermore it will also broaden our understanding of immunological responses to cancer, autoimmune diseases and infections.Read moreRead less
Viral Reservoirs:Role Of Naive T-cells In The Pathogeneisis Of T-cell Decline And Longterm Persistence Of HIV Infection.
Funder
National Health and Medical Research Council
Funding Amount
$85,716.00
Summary
Despite dramatic advances in treatment for HIV infection, HIV cannot be cured. The main reason why cure is not possible is because HIV can persist in long lived cells and these infected cells are not recognised by the immune system. This project will examine the role of a particular type of infection fighting cell, the naive T-cell, in long term persistence of HIV. The project will determine how naive T-cells are infected with HIV and what happens to these cells following HIV treatment.