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Research Topic : immune development
Scheme : NHMRC Strategic Awards
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  • Funded Activity

    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.
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    Funded Activity

    Neonatal Immunization With Pneumococcal Conjugate Vaccine In Papua New Guinea

    Funder
    National Health and Medical Research Council
    Funding Amount
    $1,181,966.00
    Summary
    One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the dev .... One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the development of immunity and response to other vaccines given to infants. This study will also provide a unique opportunity for training of PNG and Australian scientists in both countries; transfer state-of-the-art immunological technology and stimulate further collaborations on respiratory infections in the region.
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    Funded Activity

    Early Intervention To Prevent Childhood Obesity Among A Disadvantaged Population: A Home-based Randomised Controlled Tri

    Funder
    National Health and Medical Research Council
    Funding Amount
    $675,082.00
    Summary
    This intervention research will conduct a randomised controlled trial, of a community-based early childhood home visiting intervention designed to improve family and behavioural risk factors for childhood obesity and overweight. This intervention which will be developed in collaboration with the Health Promotion Unit, Child and Family Health Nurses, university academic experts and mothers in the community promises to deliver significant health and social benefits, in particular, preventing early .... This intervention research will conduct a randomised controlled trial, of a community-based early childhood home visiting intervention designed to improve family and behavioural risk factors for childhood obesity and overweight. This intervention which will be developed in collaboration with the Health Promotion Unit, Child and Family Health Nurses, university academic experts and mothers in the community promises to deliver significant health and social benefits, in particular, preventing early onset of childhood obesity. It will result in a series of recommendations for policies and practical methods for promoting healthy feeding and physical activity of infants under two years of age with particular application to families who are socially and economically disadvantaged. These policies and practical methods for preventing childhood obesity could be used across Australia.
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    Chimeric Virus-like Particles (VLPs) Displaying H1, H3 And H5 Haemagglutinins - Construction And Immunogenicity

    Funder
    National Health and Medical Research Council
    Funding Amount
    $207,543.00
    Summary
    Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can b .... Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can be produced containing each of the three most important HA types _ H1 and H3 that are currently circulating in man, and H5 (avian) that is considered a pandemic threat. VLPs will be tested for their ability to induce neutralizing antibody and cellular immune responses in mice, and for their ability to protect ferrets from influenza infection. If successful, the HA-VLP system would provide a method for the rapid production of new influenza vaccines using large-scale fermentation technology as for hepatitis B and many other vaccines, rather than eggs or cell culture as used for current influenza vaccines.
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    Funded Activity

    The Impact On Diabetes Risk Factors Of Pre & Post Traditional Lean Meat And Exercixe Interventions

    Funder
    National Health and Medical Research Council
    Funding Amount
    $44,040.00
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    Funded Activity

    Translational Control During HIV-1 Replication

    Funder
    National Health and Medical Research Council
    Funding Amount
    $398,994.00
    Summary
    HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein transla .... HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein translation from RNA are relatively poorly understood compared with the other control points of cellular gene expression, such as the synthesis of mRNA. This project examines how astrocytes rapidly detect the presence of HIV mRNA and alter their translation machinery to halt the expression of HIV protein. This host defence mechanism involves two key components; the cellular component that identifies and responds to the viral mRNA, and the structural features of the HIV mRNA that enable the cell to detect its viral origin. We will study how translation of HIV proteins requires both HIV and cellular factors. We will determine the impact of both viral RNA elements and viral RNA binding proteins on the translation of viral and cellular proteins. The contribution of the type-1 interferons that are produced in response to viral infection will be studied for their role in augmenting the inhibition of HIV protein translation. Since HIV infected astrocytes significantly contribute to the onset of AIDS dementia, we will sees a strategy to lock HIV into a dormant state in the brain and thereby prevent the neurodegenerative disease associated with HIV. We will use the anti-viral mechanism blocking HIV protein translation in astrocytes to protect other cell populations, such as the CD4+ lymphocytes, from HIV infection. These studies will also give insights into the general mechanisms for translational control of gene expression in human cells.
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    Funded Activity

    Creating B-cells To Cure Type 1 Diabetes

    Funder
    National Health and Medical Research Council
    Funding Amount
    $4,260,000.00
    Summary
    They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid .... They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid bodies (EB) - EB-derived cells, fetal pancreas and adult pancreas duct cells, will be employed to screen for and identify novel growth-differentiation factors and to optimise parameters for creating B cells in vitro or (re) generating B cells in vivo. Genetic constructs allowing regulated expression of fluorescently-tagged marker genes and growth-transcription factors will be introduced into cultured cells or transgenic mice to enable progenitor B cells to be tracked and isolated. Progenitor B cells will be typed with panels of known novel markers molecules at the gene and protein level, and gene expression profiles of tissue yielding B cells will be analysed across time to reveal further candidate markers. Molecules and methods effective in mouse systems will be applied to human ES cell-derived or pancreatic duct cells. The capacity to progenitor cells or insulin-secreting cells to ameliorate diabetes when transplanted into the testis, under the kidney capsule or into the pancreas of mouse models would represent proof-of-concept. Functional B cells derived from human ERS cells or pancreas duct cells, or growth factors that regenerate B cells in vivo, could together with appropriate immunotherapy restore B-cell function in people with type 1 diabetes.
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    Funded Activity

    Enhancing Australia's Pandemic Influenza Vaccine Output By Increasing The Yeild Of Vaccine From Eggs

    Funder
    National Health and Medical Research Council
    Funding Amount
    $251,517.00
    Summary
    Influenza epidemics cause significant morbidity and mortality, particularly amongst the young and elderly. Unlike other vaccines, a new flu vaccine formulation needs to be prepared each year from the currently circulating strain. This involves a long process of preparing new seed vaccine stock, which is then tested, manufactured and distributed. The situation is even more complicated by the ability of different influenza strains to reassort with others. An example of current major concern is the .... Influenza epidemics cause significant morbidity and mortality, particularly amongst the young and elderly. Unlike other vaccines, a new flu vaccine formulation needs to be prepared each year from the currently circulating strain. This involves a long process of preparing new seed vaccine stock, which is then tested, manufactured and distributed. The situation is even more complicated by the ability of different influenza strains to reassort with others. An example of current major concern is the possibility of deadly avian flu viruses, such as H5N1, to gain the capacity to directly infect humans by recombining with a human strain and thereby starting a new global pandemic. When the next influenza pandemic occurs, the availability of a vaccine will be of the highest priority and early supply of vaccines will save millions of lives. Since vaccination is the only sustainable defense, we face an urgent need to have the capacity to supply large numbers of vaccine doses of influenza vaccines within a short period of time. Currently, the only way of producing flu vaccines is in eggs. The speed of vaccine supply is totally dependant on the yield of vaccine from eggs and the number of eggs that can be processed at any one time. Since there are severe constraints on the number of eggs that can be simultaneously processed, the limiting factor that can be addressed is the actual yield of vaccine per egg. The aim of this project is the develop methods that allow higher levels of vaccine virus to grow in eggs. We will take a multi-pronged approach to enhancing influenza vaccine production that are directed toward increasing the capacity of eggs to promote virus replication, as well as towards the vaccine strain to boost its ability to replicate in the egg. The outcome will be an enhanced capacity for vaccine manufacturers to quickly and effectively expand vaccine supplies which will directly impact on global morbidity and mortality during a flu pandemic.
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    Funded Activity

    Examining A Core Assumption Of Policy And Services For Older Indigenous Australians

    Funder
    National Health and Medical Research Council
    Funding Amount
    $133,387.00
    Summary
    In aged care service planning, the age 50 years or over is used for the Indigenous Australian population in the same way as the age 70 years is used for the non-Indigenous population. This is based on the lower life expectancy of the Indigenous population which is presumed to result in a need for aged care services at younger ages. The underlying assumption is that Australia's Indigenous population aged over 50 has the same set of age-associated conditions and care needs as the non-Indigenous po .... In aged care service planning, the age 50 years or over is used for the Indigenous Australian population in the same way as the age 70 years is used for the non-Indigenous population. This is based on the lower life expectancy of the Indigenous population which is presumed to result in a need for aged care services at younger ages. The underlying assumption is that Australia's Indigenous population aged over 50 has the same set of age-associated conditions and care needs as the non-Indigenous population aged over 70. The evidence for this assumption is not established. It is well documented that the Indigenous population has worse health outcomes across all age groups relative to non-Indigenous Australians. However, our understanding of the details of the observed pattern is far from complete. This project seeks to compare the health status of the Indigenous population aged 50 years or over to the health status of the non-Indigenous population aged 70 years or over. The project will analyse a number of data sets to inform future directions in policy and service provision. A better understanding of these issues is fundamental to informed planning and allocation of resources, to identification of areas amenable to prevention strategies and to the development of approaches to care that meet the needs of Indigenous people.
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    Funded Activity

    Derivation Of Pancreatic Beta Cells From Embryonic Stem Cells

    Funder
    National Health and Medical Research Council
    Funding Amount
    $2,968,050.00
    Summary
    People with type 1 diabetes require regular insulin injections because the organ that normally makes insulin, the pancreas, no longer functions. The goal of this program is to derive human fetal pancreas tissues from embryonic stem cells. Such tissue could be used to replace the missing insulin producing cells in people with type 1 diabetes. The program brings together expertise in ES cell biology at Monash University and the leading diabetes research at the Walter and Eliza Hall Institute.
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