Determining The Role Of DOCK8 In CD4+ T And B Cell Differentiation And Its Implications On Autosomal Recessive Hyper IgE Syndrome (AR-HIES)
Funder
National Health and Medical Research Council
Funding Amount
$512,600.00
Summary
Autosomal recessive hyper IgE (AR-HIES) syndrome due to mutations in DOCK8 is a rare primary immunodeficiency whereby patients present with susceptibility to severe and recurrent viral infections as well as an increased risk of developing cancer, severe food and environmental allergies, and atopic disease characterised by hyper IgE and extreme eosinophilia. This grant will investigate how abnormal DOCK8 function in CD4+ T cells and B cells contributes to disease pathogenesis in AR-HIES patients.
A vaccine for hepatitis C virus (HCV) is not yet available. Immune responses that are able to protect against infection are possible, making the production of a vaccine a realistic goal. We have produced a unique HCV vaccine and are now poised to test our vaccine in novel humanised animal models. Our research will allow us to determine the immune responses responsible for providing protection against HCV. Our data will be highly significant for future HCV vaccine studies in humans.
Mechanisms And Targets Of Antibody-complement Interactions That Neutralize Malaria
Funder
National Health and Medical Research Council
Funding Amount
$647,977.00
Summary
Our project aims to identify immune mechanisms that neutralize malaria from the moment of inoculation by a mosquito, before infection can become established to prevent the development of malaria disease. Furthermore, we will discover specific targets of protective immune responses. We expect this project will provide major new advances in our knowledge of human immunity to P. falciparum malaria, one of the world’s most significant causes of mortality and morbidity, and we will use this knowledge
Determining The Essential Regulators Of Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$768,612.00
Summary
Plasma cells produce the antibodies that are essential to protect us from pathogenic microorganisms and provide the basis for the beneficial effects of vaccination. Plasma cells can also cause disease through the production of antibodies against our own body, for example in Lupus and in the blood cell cancer multiple myeloma . Our research aims to understand the genetic regulation of antibody production, with an aim to "switch off" inappropriate antibody supply in disease.
Comparing Pneumococcal Vaccines In A High Risk Population: A Randomised Controlled Trial Of Immunogenicity, Safety And Impact On Carriage Of Pneumococcal Conjugate And Polysaccharide Vaccines In Infants In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,042,670.00
Summary
Pneumococcal disease is a major cause of pneumonia and meningitis in infants in developing countries in particular resulting in an estimated 800,000 deaths each year. This project will study how well pneumococcal vaccines perform in 260 high-risk infants in Papua New Guinea. We will examine how well the vaccines stimulate protective immunity and reduce babies carrying the pneumococcal bacteria in their nose and how long this immunity lasts for. The study will inform global immunisation policy.
Functional Assays Of Immunity To Malaria In Pregnant Women
Funder
National Health and Medical Research Council
Funding Amount
$578,905.00
Summary
Pregnant women are highly susceptible to malaria due to the adhesion of infected erythrocytes to the placenta. Antibodies to these infected erythrocytes can block their placental adhesion and/or facilitate their clearance by immune cells, improving pregnancy outcomes. We aim at informing vaccine design by better understanding the placental adhesion mechanisms and identifying targets of protective immunity as well as antibody correlates of protection from placental malaria and its consequences.
Delineating Aberrant Adaptive Immune Responses Due To Germline Mutations In The PI3K Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$975,476.00
Summary
Activation of immune cells is required to generate appropriate immune responses that protect is from disease caused by pathogens. The inability to receive the correct type of signals causes immunodeficiency. The PI3 kinase pathway is central to immune cell activation – and genetic errors in this pathwat compromise the functioning of immune cells. We will investigate the nature of these defects and pursue avenues of overcoming them using pharmacological inhibitors of the PI3K pathway.
Identification Of Novel HCV-specific B Cell Epitopes Which Induce Broad Neutralising Antibodies
Funder
National Health and Medical Research Council
Funding Amount
$482,480.00
Summary
This research project will study humans who have been exposed to multiple Hepatitis C virus infections. We will be examining their immune response with the aim to identify subjects with antibodies that are able to neutralise a diverse range of hepatitis C virus variants. These antibodies will be used to identify novel targets for a vaccine directed against Hepatitis C virus.
Epigenetic Mechanisms That Regulate B Cell Differentiation And Memory B Cell Persistence To Provide Long-term Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$318,196.00
Summary
Memory immune cells remember antigens that have previously induced an immune response, and the ability of these cells to rapidly clear pathogens has led to successful vaccination programs. This project will study epigenetic changes during the formation of immune memory that results in protection against foreign antigens. Understanding these processes will assist in creating more effective vaccines and treatments for patients with immune disorders.
The immune system usually rapidly responds to eradicate infectious pathogens. However patients with mutations in the gene PI3KCD, which is important for delivering messages within immune cells, are unable to control infections with some bacteria and viruses. We will study the effects of these mutations on B cells, the immune cells produce antibodies that bind to and remove pathogens from our body. This will explain some of the clinical features of this disease and reveal potential new treatments