In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extende ....In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extended periods. We intend to test the ability of this vaccine to persist and persistently produce effective CD8 T cells not only systemically in the blood system but also at mucosal surfaces, where HIV usually gains entry during sexual intercourse.Read moreRead less
Optimising Immunity Towards Cancers By Vaccination.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
In this project we will be studying the mechanisms of how an efficient anti cancer vaccine could be generated. We will be using cervical cancer associated human papillomavirus type 16 E7 protein as the model protein in an experimental vaccine model in mice. The results obtained from this project not only able us to design better vaccines against cervical cancers in women but against many other cancers and viruses.
Impact Of Influenza A Infection On T Cell-mediated Immunity To Pulmonary Tuberculosis.
Funder
National Health and Medical Research Council
Funding Amount
$488,058.00
Summary
Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of B ....Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of BCG.Read moreRead less
Discovery Of Long CD8+ T Cell Epitopes Uncovers A Hidden Reservoir Of Immunodominant, Anti-tumour Responses
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
Stimulating killer T cells to eliminate tumours has been one of the ultimate yet elusive goals of cancer vaccine development. Vaccines aimed at stimulating killer T cells are similar to those generated under natural conditions. However, special strategies are needed to vaccinate beneficial killer T cells that are not normally part of the natural immunity. In this project, we will explore such a scenario and dissect the related mechanisms contributing to such differential immune outcomes.
Immunodominance In Vaccinia Virus And Recombinant Vaccinia Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$388,455.00
Summary
When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do ....When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do not understand well, T cells that recognize only a few out of the many peptides will dominate an entire immune response. As a result, immune responses are focused in such a way that they recognize only a tiny portion of an invading microbe. Focusing of immune responses also occurs during immunization with vaccines. Some new, genetically engineered vaccines use a harmless microbe to carry small parts of more dangerous pathogens. The parts chosen will not cause any disease by themselves, so the whole vaccine is safe. Vaccines built in this way are in clinical trials for diseases such as AIDS and malaria, but do not work as well as was hoped. These new vaccines are largely made up of the carrier and the parts of the microbe we wish to immunize against (e.g. a part of the AIDS virus) will be only a small fraction of the whole vaccine. Ideally we would like the immune system to focus on this small part of our choosing, but the few studies done suggest that this is not the case. In this project we will study vaccines that use a carrier called vaccinia virus. We will test to what extent immune responses are focused inappropriately. We will then genetically alter the virus and use new immunisation strategies to try and shift the focus of the immune response so that it targets the right parts of the vaccine. The ultimate aim is to improve vaccines, but in the process we may learn more about how the immune system chooses its targets.Read moreRead less
Novel Generic Vaccine Approaches Applied For The Prevention Of Hepatitis C And Influenza Virus Infections.
Funder
National Health and Medical Research Council
Funding Amount
$392,328.00
Summary
For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are maj ....For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are major human pathogens. HCV has infected 200 million people worldwide, and there is no effective vaccine available. Influenza continues to affect thousands of people each year causing epidemics with severe morbidity and considerable mortality. Current influenza vaccines are mostly inactivated formulations and they exhibit poor immunogenicity in immunological naive persons such as children and in the elderly. The influenza vaccines are not optimal for stimulation of cell-mediated immunity. We propose to use particulate antigens as a delivery platform for influenza and HCV-specific epitopes with the focus to develop approaches to target various HCV and influenza strains, including H5N1 bird influenza. We have successfully produced modified VLPs containing HCV-specific sequences, which are able to induce anti-HCV antibodies with neutralising capacity. We hypothesise that the design of VLPs with an appropriate set of HCV-specific antigens will enhance the neutralising capacity of anti-HCV sera and this may overcome strain specificity. This application will exploit a prototype delivery system to induce antibody and also cellular responses against a variety of HCV- and influenza specific target sequences (epitopes). The outcome of this study will be a prototype multivalent vaccine to a range of HCV- and influenza-specific epitopes. As a delivery system this will be ideal for vaccination against agents that are highly variable.Read moreRead less
Molecular Approaches To Developing Subunit Vaccines With Improved Efficacy Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to ....Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to induce immune responses in animals and humans. We will produce vaccines that are made from 13 of these important proteins. Using a laboratory animal model that closely mimics human tuberculosis infection, together with sophisticated immunological techniques, we will determine if these vaccines stimulate the right immune response to fight tuberculosis and prevent infection. In addition, we will exploit molecules known to boost immune responses to optimise these vaccines. Further we will study the recently sequenced genome of the tuberculosis bacterium to identify new proteins that may be included in these novel anti-tuberculosis vaccines. This is an internationally competitive project and our team is at the forefront of this research effort. A new, effective tuberculosis vaccine would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Development Of Hepatitis B Surface Antigen As A Generic Vector For The Delivery Of Foreign CTL Epitopes.
Funder
National Health and Medical Research Council
Funding Amount
$439,642.00
Summary
Many kinds of cancer and infections display unique proteins which the body's immune system can recognise as ' foreign', and mount an immune response which, if correctly harnessed, will kill the cancer or infected cells . A way to harness the immune response is to vaccinate with these unique proteins. However, new ways need to be found to deliver the unique proteins to produce the maximal possible anti- cancer or pathogen response, and one that is long lived. In particular one needs to stimulate ....Many kinds of cancer and infections display unique proteins which the body's immune system can recognise as ' foreign', and mount an immune response which, if correctly harnessed, will kill the cancer or infected cells . A way to harness the immune response is to vaccinate with these unique proteins. However, new ways need to be found to deliver the unique proteins to produce the maximal possible anti- cancer or pathogen response, and one that is long lived. In particular one needs to stimulate the cellular arm of the immune response to produce killer cells named CTLs which specifically kill cancer or infected cells. In this project we plan to use an already-licensed human vaccine - the Hepatitis B surface antigen vaccine , or HBsAG, - and genetically modify it to contain important regions of cancer or pathogen proteins termed 'epitopes'. We surmise that immunisation with these modified HBsAg will elicit powerful CTL responses which will killer cancer or infected cells.Read moreRead less