Pandemic Influenza Vaccine: Exploiting The Conserved HA Cleavage Site
Funder
National Health and Medical Research Council
Funding Amount
$243,300.00
Summary
Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preve ....Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preventing the viral spike protein from being cleaved and remain immature. This idea is particularly suited to fight the bird flu, as all pathogenic bird influenza viruses cleave HA spike proteins within the infected cell.Read moreRead less
A Preclinical Model Of Pig Islet Xenotransplantation As Treatment For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$4,380,000.00
Summary
The object of this multi-disciplinary program grant is to develop a source of pig insulin secreting tissue that will be used to treat type 1 diabetic patients. At present the number of diabetic patients that would benefit from islet transplantation far outnumber any human source of this tissue. Pigs that have been genetically altered to avoid rejection and enhance survival could overcome this donor shortage problem.. It is our belief that with the appropriate genetic modification pig insulin-sec ....The object of this multi-disciplinary program grant is to develop a source of pig insulin secreting tissue that will be used to treat type 1 diabetic patients. At present the number of diabetic patients that would benefit from islet transplantation far outnumber any human source of this tissue. Pigs that have been genetically altered to avoid rejection and enhance survival could overcome this donor shortage problem.. It is our belief that with the appropriate genetic modification pig insulin-secreting tissue can avoid the aggressive rejection response that occurs with xenographs and provide normal blood glucose control without insulin. This project concentrates on the five main issues that need to be overcome before pig insulin-secreting tissue can be used in diabetics. These are: identifying the best source of insulin secreting tissue to use; adult islets, newborn or foetal islet cell clusters; overcoming the strong rejection response to pig tissue; identifying a safe and effective immunosuppressive regime; producing a new types of genetically modified pigs that will provide islets tissue that will work in humans; and demonstrating that pig islet transplantation will not pose undue infective risks for the patient or community. This truly collaborative program grant has brought together a large group of investigators with strong research records in diabetes, islet transplantation, xenotransplantation, pig transgenesis and pig genetics and includes scientists and clinicians who look after diabetic patients. Unique pig resources will be used including genetically manipulated pigs that have been shown to avoid some of the rejection mechanisms associated with transplanting pig tissue. There is a captive-bred baboon colony that provided a unique model of diabetes. A world class pig transgenesis facility has been enlisted to generate new lines of genetically altered pigs as new data is produced within the group. Finally because of the involvement of the National Pancreas Transplant Unit any proven therapeutic strategy can be brought quickly to clinical trials.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
Enterovirus 71 In The Asia-Pacific Region: Reverse Genetic Approaches To Virus Surveillance And Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$690,833.00
Summary
In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop ....In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop a genetically defined, live attenuated vaccine strain. Candidate vaccine strains will be tested for their effectiveness in both cell culture-based and animal models.Read moreRead less
Collaborative Ovarian, Prostate And Breast Gene-environment Study (COGS)
Funder
National Health and Medical Research Council
Funding Amount
$447,383.00
Summary
The EU-COGS application has arisen from genome wide scans that identify common genetic variants associated with breast, ovarian and prostate cancer risk. Our studies contributed 50% of DNA samples to the prostate cancer genome wide scan. COGS will now measure these variants in a large number of cases and controls from an international consortium of studies to test whether genetic risks are modified by other genes or lifestyle factors. This will better define genetic risks and identify men at inc ....The EU-COGS application has arisen from genome wide scans that identify common genetic variants associated with breast, ovarian and prostate cancer risk. Our studies contributed 50% of DNA samples to the prostate cancer genome wide scan. COGS will now measure these variants in a large number of cases and controls from an international consortium of studies to test whether genetic risks are modified by other genes or lifestyle factors. This will better define genetic risks and identify men at increased risk who should be the focus of appropriate screening and prevention strategies. Australian participation in the prostate cancer genome wide scan helped to identify a number of genetic variants associated with prostate cancer risk. The aim of EU-COGS, which needs large numbers of samples with epidemiological, tumour pathology and clinical information, is to determine whether these genetic variants act singly or together and the extent to which lifestyle and environmental factors can modify the genetic risk. Our contribution of >10% of the total DNA samples to COGS will enable us to understand how such genetic risks can be modified in the Australian environmental context.Read moreRead less
Establishment Of A Latrobe Valley Power Industry Cohort And Biospecimen Bank For The Study Of Asbestos Related Disease
Funder
National Health and Medical Research Council
Funding Amount
$614,466.00
Summary
The Latrobe Valley has been the site of Victoria�s electricity generation since the 1920�s. Very large amounts of asbestos were used in the construction of power stations and housing for the workers employed to build and operate them. Asbestos is known to cause a tumour of the lining of the lung cavity called mesothelioma. Mesothelioma is a highly debilitating tumour, with a median survival as low as seven months following diagnosis. Mesothelioma can occur in asbestos exposed individuals up to f ....The Latrobe Valley has been the site of Victoria�s electricity generation since the 1920�s. Very large amounts of asbestos were used in the construction of power stations and housing for the workers employed to build and operate them. Asbestos is known to cause a tumour of the lining of the lung cavity called mesothelioma. Mesothelioma is a highly debilitating tumour, with a median survival as low as seven months following diagnosis. Mesothelioma can occur in asbestos exposed individuals up to forty years following exposure, and as such, the peak number of cases of mesothelioma is not expected in Australia for another 10-20 years. The incidence of mesothelioma in the Latrobe Valley is several fold the state average. We will recruit a cohort of 5000 asbestos exposed former power industry workers, and provide information, support and smoking cessation campaigns. For 1000 of the most highly exposed we will offer annual testing for mesothelin, a protein in the blood which may indicate the presence of mesothelioma prior to a clinical diagnosis.Read moreRead less