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HIV currently infects ~40 million people world-wide, causing ~3 million deaths in 2003, mainly in the world's poorest countries. A cheap, effective vaccine seems the best means of preventing the spread of the epidemic. The two main approaches to vaccination are either to make antibodies (which bind to and inactivate the virus), or killer T cells (which kill infected cells). Many of these vaccines are now being tested in monkeys. The results of killer T cell vaccination trials have been both enco ....HIV currently infects ~40 million people world-wide, causing ~3 million deaths in 2003, mainly in the world's poorest countries. A cheap, effective vaccine seems the best means of preventing the spread of the epidemic. The two main approaches to vaccination are either to make antibodies (which bind to and inactivate the virus), or killer T cells (which kill infected cells). Many of these vaccines are now being tested in monkeys. The results of killer T cell vaccination trials have been both encouraging and disappointing. The vaccines do not appear able to prevent the monkeys from getting infected with the virus. However, in many cases even though the monkeys become infected with HIV, they do not get the usual disease associated with AIDS, and hence live with rather than die from this infection. The aims of this project are to use statistical analysis, and more complex mathematical and computer models to try to analyse the data generated by these vaccine trials and to understand how these partially effective vaccines help control virus. For example, even if a vaccine does not prevent infection, we can investigate whether it slowed viral growth, or increased killing of infected cells, and if so, whether an increase in this response could be effective. In preliminary work we have analysed data from a vaccination trial performed in Boston. The results of this study suggest that the reason vaccinated monkeys still become infected is that the killer T cells produced by the vaccine do not appear to activate for the first 10 days of infection. In these first 10 days the virus grows normally and is able to establish a foothold for continuing infection. By contrast, we find that antibodies act extremely early after infection. The methods we propose have not been used before to study vaccines, and by studying the kinetics of the virus and immune response from a large number of vaccine trials we hope to help identify the optimal vaccine design.Read moreRead less
A New Scrambled Antigen Vaccine (SAVINE) Approach: Proof-of-concept In Non-human Primates For HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$120,700.00
Summary
The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of H ....The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of HIV-1 to provide universal coverage of the major HIV-1 strains for a global population. The synthetic systematically designed HIV-1 vaccine will be delivered using our newly developed prime-boost immunisation regime that induces particularly high levels of cell-mediated immunity.Read moreRead less
This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology ....This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology, the establishment of the only PC3-level nonhuman primate facility in the Southern hemisphere, T cell immunogenicity of the DNA-viral vector prime-boost vaccine regimens and ground-breaking research on cytokine co-expressing viral vector vaccines. The Principle Investigators also have a record of substantial achievement in relation to HIV and T cell biology as well as novel vaccination technologies. There is a strong history of successful collaboration among this group leading to the award of major NIH funding.Read moreRead less
Determinants Of The Clearance Of HIV Infected Cells By Successful AIDS Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$188,500.00
Summary
A vaccine is urgently needed to halt the global AIDS epidemic caused by HIV infection. We have previously demonstrated that new generation vaccine technology can prevent HIV infection. DNA and fowlpoxviruses vaccines are designed to carry in parts of HIV and induce very vigorous immune defences to be mounted against HIV. The proposal seeks to understand why these vaccines work, their limitations, and to help guide further improvements to these vaccines. In particular, we will look at how these v ....A vaccine is urgently needed to halt the global AIDS epidemic caused by HIV infection. We have previously demonstrated that new generation vaccine technology can prevent HIV infection. DNA and fowlpoxviruses vaccines are designed to carry in parts of HIV and induce very vigorous immune defences to be mounted against HIV. The proposal seeks to understand why these vaccines work, their limitations, and to help guide further improvements to these vaccines. In particular, we will look at how these vaccines clear cells that become infected with the virus and which are the most important cells that do this. We will also look at whether HIV can hide away in latent forms despite seemingly successful vaccination. Importantly, we will address whether these vaccines should limit the spread of HIV between people, an important public health goal of successful vaccines.Read moreRead less
The development of vaccines and better treatments for HIV-AIDS and Hepatitis C are urgent global health priorities. This Program will undertake studies to better understand effective immunity against HIV and hepatitis C, allowing the rational design and testing of novel vaccines and treatments. The Program brings together a team of researchers with skills in basic virology and immunology with those providing expertise in translating findings in the laboratory into human clinical trials.
Comparative Effectiveness Of Vaccine-induced SIV-specific CD8 T Cells
Funder
National Health and Medical Research Council
Funding Amount
$607,797.00
Summary
A HIV vaccine remains elusive. Although killer T cell immunity can provide partial protection from HIV disease, we don't know the best type of killer T cells to induce by vaccination. This project compares multiple HIV vaccine strategies in macaques. We will carefully study the quality of killer T cell immunity induced using novel and cutting-edge assays. We will identify the requirements for effective killer T cell immunity to HIV.