Autoimmune Polyendocrine Syndrome Type 1 - A Rare Disorder Of Childhood As A Model Of Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$506,943.00
Summary
This project will analyse the mechanisms and causes of diabetes and other autoimmune diseases where the immune system damages particular organs of the body. Diabetes is a national health priority, and autoimmune diseases collectively affect one in every twenty Australians. The project will focus on a recently discovered gene, Autoimmune Regulator (AIRE) that is crucial for protection against autoimmune disease, which Prof Goodnow's team has shown to stop forbidden clones of T lymphocytes in the ....This project will analyse the mechanisms and causes of diabetes and other autoimmune diseases where the immune system damages particular organs of the body. Diabetes is a national health priority, and autoimmune diseases collectively affect one in every twenty Australians. The project will focus on a recently discovered gene, Autoimmune Regulator (AIRE) that is crucial for protection against autoimmune disease, which Prof Goodnow's team has shown to stop forbidden clones of T lymphocytes in the immune system from attacking our own organs. Inherited defects in the AIRE gene cause a devastating illness, Autoimmune Polyendocrine Syndrome 1, and provide an unparalleled insight into mechanisms of common autoimmune diseases such as Type 1 diabetes, thyroid diseases, pernicious anemia, and Addison's disease. By joining forces with Dr H Scott and a multidisciplinary consortium in Europe, Prof Goodnow's team will investigate how the processes controlled by the AIRE gene cooperate with other genes and mechanisms to prevent autoimmune disease. The work will chart the different control systems that normally protect us from autoimmune diseases, and provide a rational basis for developing new ways to treat and prevent autoimmune diseases. The NHMRC funding enables two leading Australian groups at The Australian National University and at the Walter and Eliza Hall Institute to amplify their world-leading individual efforts by leveraging a set of complementary technologies and clinical resources of an interdisciplinary team in Europe. Goodnow's team has already proved the benefit of this type of Australian-European collaboration. Their work discovering the function of the AIRE gene in stopping forbidden T cells depended on a close collaboration with the genetics group in Finland led by Prof Leena Peltonen, whose team had originally discovered the AIRE gene as part of a large European consortium. Scott's team was part of a parallel European-Japanese consortium that discovered the AIRE gene at the same time. The EURAPS project will build on these collaborative discoveries to chart the mechanisms of autoimmune disease and how they can be cured or prevented.The NHMRC funding for the Australian teams is amplified to a multiplier of twenty-fold by European funding for the overall EURAPS project. This represents a strategic investment to ensure Australian health research remains at the forefront of advances in prevention and treatment of chronic diseases.Read moreRead less
Genomic And Proteomic Profiling Of Dendritic Cell Heterogeneity
Funder
National Health and Medical Research Council
Funding Amount
$1,971,250.00
Summary
Dendritic cells (DC) present antigens to T cells and regulate immunity and tolerance. DC are heterogeneous, comprising seven functionally distinct subsets. We will use genomics and proteomics to identify the plasma membrane and endosomal proteins that underpin this functional heterogeneity. Such proteins are potential targets for improved protocols of vaccination and prevention of autoimmunity. This project will thus provide further opportunities for high-quality research and commercialisation.
A link between periodontal disease, inflammation of the gums, and cardiovascular disease has been suggested in recent studies, however the evidence remains uncertain. Supporting the link are data that inflammation predisposes to atherosclerosis and heart attacks. Patients in the PERICAR study will have blood tests before and after periodontal treatment so that researchers can study whether treatment reduces factors in the blood that have previously been shown to indicate the risk of cardiovascul ....A link between periodontal disease, inflammation of the gums, and cardiovascular disease has been suggested in recent studies, however the evidence remains uncertain. Supporting the link are data that inflammation predisposes to atherosclerosis and heart attacks. Patients in the PERICAR study will have blood tests before and after periodontal treatment so that researchers can study whether treatment reduces factors in the blood that have previously been shown to indicate the risk of cardiovascular disease. This study will provide further clues to this potentially very important and treatable relationship.Read moreRead less
The Use Of Inulin-based Adjuvants To Enhance The Effectiveness And Population Coverage Of Influenza Vaccination
Funder
National Health and Medical Research Council
Funding Amount
$250,393.00
Summary
A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This tec ....A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This technology is known as a vaccine adjuvant and we have developed a unique adjuvant based on a natural plant sugar called inulin that has the potential to dramatically enhance existing and new flu vaccines.Read moreRead less
Mucosal Vaccine For Influenza On Inactivated Virus And Mannan
Funder
National Health and Medical Research Council
Funding Amount
$131,993.00
Summary
Influenza is a respiratory disease that causes significant morbidity and mortality worldwide. Current influenza vaccines are a preparation of three currently circulating inactivated influenza strains that induces an antibody response that can combat the virus and therefore infection. Despite the availability of a vaccine new approaches are needed to increase the activity, usage and distribution. To this end several approaches based on using additional agents to increase the immunogenicity and ne ....Influenza is a respiratory disease that causes significant morbidity and mortality worldwide. Current influenza vaccines are a preparation of three currently circulating inactivated influenza strains that induces an antibody response that can combat the virus and therefore infection. Despite the availability of a vaccine new approaches are needed to increase the activity, usage and distribution. To this end several approaches based on using additional agents to increase the immunogenicity and needle free delivery are being explored. We have a natural sugar based compound that can be used to increase the body's immunity to cancers and infectious agents such as bacteria and viruses. When these preparations are applied into the nostril of mice they generate antibody responses to the infectious agent in the lungs, gut, tears, saliva that can act as a barrier to infectious agents. We are incorporating an inactive flu virus with this natural sugar to investigate if it produces antibody that can protect mice and ferrets from the flu virus. This method will be first tried with the human flu virus and if successful will be tried with the bird flu virus. If the preparation can protect mice and ferrets from human or bird flu infection it could develop into a human vaccine against bird flu. Since it can be administered by the nose it will be widely used and can be used readily without qualified personnel in the case of a pandemic.Read moreRead less
Assessment Of Alpha-galactosylceramide As A Novel Adjuvant For Pandemic Influenza: A Virua Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$220,042.00
Summary
The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, ....The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, however there are no commercially available avian influenza vaccines available. Moreover, recent evidence suggests current vaccines strategies may be less than effective. This proposal aims to evaluate the efficacy of a novel vaccine strategy that promotes immune protection against a potential pandemic influenza strain.Read moreRead less
This study will examine cellular immunity to the avian H5 influenza in people who have been previously infected with the currently circulating strains of H1 and H3 influenza, or in those who have been recently vaccinated with current influenza vaccines. This will give us an idea if there is any cross reactive immunity that may assist in developing immunity to pandemic strains of avian influenza, or may provide help in making antibody responses sooner to avian influenza vaccines once they are dev ....This study will examine cellular immunity to the avian H5 influenza in people who have been previously infected with the currently circulating strains of H1 and H3 influenza, or in those who have been recently vaccinated with current influenza vaccines. This will give us an idea if there is any cross reactive immunity that may assist in developing immunity to pandemic strains of avian influenza, or may provide help in making antibody responses sooner to avian influenza vaccines once they are developed. We will also establish assays to determine how immunogenic some new avian influenza vaccines are in mice.Read moreRead less
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
Novel Probiotics And Naturally-sourced Extracts As Treatment Strategies For Chemotherapy-induced
Funder
National Health and Medical Research Council
Funding Amount
$322,183.00
Summary
Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have be ....Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have been anecdotal claims of medicinal application for so-called ‘bioactive’ extracts and formulations derived from a range of mammalian, marine and plant sources. Specifically, Lyprinol (an extract derived from the New Zealand Green-Lipped Mussel), Emu Oil (derived from Emu meat) and the herbal extract Iberogast, have been reported to possess antiinflammatory properties. Indeed, these agents are used widely for the adjunctive relief of symptoms associated with arthritis and joint pain. However, these agents have yet to be tested for their potential to treat or prevent intestinal mucositis. For the first time, utilizing proven, controlled animal model systems, the current submission will explore the therapeutic potential of these agents, alone and in combination with indicated probiotics, for their capacity to treat or prevent mucositis. Should efficacy be demonstrated, a potential mechanism of action will be sought by investigating effects on intestinal stem cells.Read moreRead less