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We know that many parts of viruses are displayed to the immune system, but infection can also result in the display of fragments of our body's own proteins (self-peptides). We will apply cutting-edge technology to find all the virus- and self-peptides that are recognised by the immune system during infection with a vaccine virus and influenza virus. This will help us understand how the body fights infection and perhaps why infection can sometimes start autoimmune diseases.
CD8+ T cells provide us with protection against viruses and can also mediate potent anti-tumour effects. Understanding the signals that initiate and sustain an effective CD8+ T cell response is important if we are to intervene in diseases where CD8+ T cell function is defective. We will study patients with inherited gene defects that disrupt some of the signals that T cells receive to determine the role those signals usually play in instructing CD8+ T cells to fight viral infection.
A New Approach To The Design And Evaluation Of T Cell Vaccines For Cancer And Infectious Disease.
Funder
National Health and Medical Research Council
Funding Amount
$394,137.00
Summary
Special white blood cells called dendritic cells teach the immune system to fight cancer and are a key component of therapeutic cancer vaccines. We identified a subtype of human dendritic cell that is predicted to be the most effective at mounting anti-cancer immune responses. We developed a novel antibody specific for these dendritic cells that can be used to deliver the vaccine directly to them and will use this to construct and validate a novel vaccine for cancer and viral infections.
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.
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date
The Role Of Kdm1a In Epigenetic Regulation Of Virus-specific T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$510,982.00
Summary
Recovery from infection, or vaccination, results in the establishment of protective immunity that persists for the life of an individual. Unfortunately, our understanding of how protective immunity is established and maintained after infection or vaccination is lacking. This proposal will determine whether specific enzymes involved in rewriting the genetic blueprint are key for establishing and maintaining this protective capacity. Understanding these mechanisms has implications for vaccination ....Recovery from infection, or vaccination, results in the establishment of protective immunity that persists for the life of an individual. Unfortunately, our understanding of how protective immunity is established and maintained after infection or vaccination is lacking. This proposal will determine whether specific enzymes involved in rewriting the genetic blueprint are key for establishing and maintaining this protective capacity. Understanding these mechanisms has implications for vaccination and improved immunotherapy strategies for cancer.Read moreRead less
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
Viral Antigen Presentation Kinetics And Memory T Cell Inflation
Funder
National Health and Medical Research Council
Funding Amount
$503,753.00
Summary
The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other path ....The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other pathogens.Read moreRead less
Determinants Of CTL Recruitment Into The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$474,647.00
Summary
The size of CD8+ T cell (CTL) responses is central to their efficacy in virus control, and can be substantially influenced by how effectively they are recruited and expand after infection. This study will determine the impact of both CTL characteristics and antigen abundance on CTL recruitment and expansion after infection. Understanding the nature of these influences will enable a more informed approach to the clinical manipulation of CTL responses.
Lodging Resident Memory T Cells Along The Respiratory Tract As An Approach To Protect Against Influenza Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$626,555.00
Summary
We have developed methods to deposit highly protective influenza fighting cells along the respiratory tract and we will apply these principles to develop better influenza virus vaccines