A Dendritic Cell Subset Targeting Approach For Generating Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$678,492.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
Detailed Investigation Of The Humoral Immune Response To HCV To Identify Diagnostic And Prognostic Serological Markers
Funder
National Health and Medical Research Council
Funding Amount
$387,466.00
Summary
The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the d ....The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the different stages of infection. The expected outcomes of this study include the identification of a marker of recent Hepatitis C infection. This will permit accurate epidemiological monitoring of Hepatitis C, better design of programs to control the spread, trace outbreaks and manage treatment programs. The identification of a marker capable of predicting the clinical outcome of infection would be invaluable to clinicians, because following acute infection with Hepatitis C, 20 to 30% of individuals will resolve their infection without the need for therapeutic intervention. The information obtained in this study will also lead to a better interpretation of diagnostic laboratory findings, improving our ability to provide clear and accurate reports to blood donors and consequently enhance the Australian blood supply in terms of safety and donor retention.Read moreRead less
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.
Using Immunological Principles To Inform Malaria Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$577,763.00
Summary
Malaria kills ~420,000 people each year worldwide. While a vaccine does exist, efficacy is poor and protection wanes rapidly. We have made breakthroughs in understanding the immune response to malaria that allow us to design a new generation of malaria vaccines. Based on this we aim to generate a vaccine that induces sustained levels of high-quality antibodies targeting multiple targets on the parasite and so can provide sustained long-term protection.
Mechanisms Of B Cell Immunodominance To Influenza Virus
Funder
National Health and Medical Research Council
Funding Amount
$617,611.00
Summary
Current influenza vaccines elicit poor protection against viruses undergoing rapid change or emerging from animal reservoirs. We will define the basis for why highly conserved sites of virus vulnerability, such as the hemagglutinin "stem" domain, are poorly targeted by current vaccines and will assess novel hemagglutinin stem-based vaccines in macaque models of human influenza. Our results will guide the rational design of next-generation vaccines for influenza.
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.
Identifying The Molecular Basis Of Memory B Cell Function And Human Immunoglobulin E Memory Via Hyper Immunoglobulin E Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$96,009.00
Summary
Memory B cells generate rapid and potent antibody responses to known threats. The molecular basis for this is unknown, but defects increase the risk of infection, autoimmunity, and allergy. Autoimmunity and allergy are often mediated by a poorly understood antibody subclass, immunoglobulin E (IgE). My project will use emerging single-cell technologies to reveal the molecular mechanisms of antibody memory and IgE regulation, enabling the design of superior vaccines and immunomodulatory therapy.
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.