Generation And Persistence Of Effective T Cell Immunity Towards Seasonal And Pandemic Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$451,716.00
Summary
Introduction of a new influenza strain into human circulation leads to a rapid global spread of the virus (e.g. H1N1 2009 pandemic) due to minimal antibody immunity. Established T cell immunity towards conserved viral regions promotes rapid recovery. However, it is unclear what determines the effective T cell immunity towards influenza. We will define the optimal human T cell populations, with the ultimate goal of improving vaccine design so it protects against seasonal and pandemic strains.
Understanding And Controlling Viral Escape In Influenza
Funder
National Health and Medical Research Council
Funding Amount
$433,156.00
Summary
Introduction of a new influenza strain into human circulation leads to a rapid global spread of the virus (e.g. H1N1-09 pandemic) due to minimal antibody immunity. Established T-cell immunity towards conserved viral regions promotes rapid recovery. However, the protective immunity exerts pressure on influenza, leading to "escape" mutations. We will unravel how the viral mutants emerge and propose strategies for T cell-based protective immunity and vaccine design against influenza.
Visualisation Of Gamma-delta T Cell Responses In Cutaneous Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Mycobacterial infections remain a major burden of modern society. This proposal aims to define the role of an understudied immune cell subset, gamma-delta T cells, in the response against mycobacteria. We will use cutting-edge multi-photon imaging to track these cells in real-time directly within infected tissues. This will facilitate generating a new vista of anti-mycobacterial immune responses and may aid the development of improved vaccines.
Development And Validation Of A Latent Tuberculosis Diagnostic
Funder
National Health and Medical Research Council
Funding Amount
$534,865.00
Summary
Globally, tuberculosis is a leading cause of death with 9.6 million new diagnoses in 2014. The diagnosis of latent TB infection is important, but is difficult to make because current assays are suboptimal. We have developed a very simple assay which detects responses to TB antigens by co-expression of two surface markers expressed by CD4+ T cells. We propose to develop this into a highly standardised kit for the diagnosis of TB with our commercial partner Cytognos.
CD4+ T Cell-independent Immunity Against Salmonellae
Funder
National Health and Medical Research Council
Funding Amount
$550,226.00
Summary
Salmonella typhimurium is an important pathogen in both developed and developing countries where it causes significant HIV-linked morbidity. There is a pressing need to understand how immunity might be established against this organism that will function when the patient is immunocompromised either through age or through a comorbidity like HIV.
Gamma-ray Inactivated Influenza A Virus Vaccine For Cross-protective T Cell Immunity
Funder
National Health and Medical Research Council
Funding Amount
$239,963.00
Summary
Although there are new antiviral drugs that appear to be effective against influenza virus, the far more costeffective and efficient means to combat an influenza pandemic would be by vaccination. Current influenza vaccines employ virus preparations that are inactivated by chemical treatment. The inactivated vaccines, which function mostly by inducing antibody against the virus, have to be reformulated almost every year to take account of the changing virus because the antibodies recognize the vi ....Although there are new antiviral drugs that appear to be effective against influenza virus, the far more costeffective and efficient means to combat an influenza pandemic would be by vaccination. Current influenza vaccines employ virus preparations that are inactivated by chemical treatment. The inactivated vaccines, which function mostly by inducing antibody against the virus, have to be reformulated almost every year to take account of the changing virus because the antibodies recognize the viral surface which is prone to mutation. Accordingly, in terms of the threatening H5N1 avian influenza pandemic, it is not known if an inactivated vaccine based on the circulating H5N1 strain will be effective if the virus mutates to adapt to efficient growth and spread in the human population. In contrast to the antibody response against influenza virus, the cytotoxic T cell response is broadly crossreactive between heterologous influenza virus strains. Live virus infection efficiently induces cytotoxic T cell immunity which plays an important role in reducing disease severity and mortality following infection with a second, heterologous influenza virus, although infection per se is not prevented. Accordingly, vaccination strategies that elicit cytotoxic T cell memory should be given urgent consideration in the preparation against an influenza pandemic. We have found that the use of gamma-irradiation (in contrast to chemical treatment) for the preparation of inactivated experimental vaccines against influenza and other viruses does not destroy the ability of the vaccines to elicit cytotoxic T cell immunity. The gamma-ray inactivated vaccines conferred protection against lethal challenge with heterologous influenza virus strains in mice. This proposal is aimed at extending this novel finding to avian influenza viruses and to uncover the mechanisms involved in the cytotoxic T cell immunogenicity of gamma-ray inactivated vaccines.Read moreRead less
Enhancement Of Mucosal Immunity And CTL Avidity Against HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$553,070.00
Summary
Production of strong antiviral immunity at the local mucosa (genito-rectal track) is essential for protection against HIV-AIDS. We believe that expression of small hormone-like molecules known as Th2 cytokines IL-4-IL-13 negatively influence the generation of protective immunity against HIV. Thus we aim to counteract these effects by co-expressing proteins known as chemokines together with vaccine antigens to improve the quality of mucosal vaccine immunity.
Immune Correlates Of Early Corticosteroid Therapy In Vietnamese Children And Young Adults With Dengue
Funder
National Health and Medical Research Council
Funding Amount
$467,073.00
Summary
Dengue is a globally important infectious disease. This study will seek to understand how corticosteroids, an immune modulating class of drug, effect the immune responses in children with dengue. The basis for this study is a randomised controlled trial at a large hospital in Viet Nam that treats many patients with dengue. We expect to obtain the laboratory evidence needed to support further clinical trials of this drug and in doing so we will improve our understanding of dengue.