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
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.