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.
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.
Leptin As A Natural Regulator Of TFH Cell Differentiation And Vaccination Response
Funder
National Health and Medical Research Council
Funding Amount
$594,901.00
Summary
Follicular helper T (Tfh) cells constitute a CD4+ T cell subset that plays an instrumental role to support protective antibody responses in infection and vaccination. Although malnutrition is associated with poor vaccine responses and increased risks of infections, the mechanism is poorly understood. We will investigate the mechanism by which leptin, a hormone secreted by adipose cells, regulates Tfh cell function and vaccination response.
Tracking B Cell And Neutralising Antibody Responses In Hepatitis C Virus Infections
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Hepatitis C virus is one of the most significant human pathogens. There is no vaccine for HCV, and the antiviral treatment is expensive and does not stop reinfection. This project will study how the immune system of people infected with HCV generates antibodies to clear the virus. This will inform research efforts to design successful preventative vaccine to protect against this viral pathogen.
Sytemic And Mucosal Functional Antibodies In Protection Against HIV
Funder
National Health and Medical Research Council
Funding Amount
$559,501.00
Summary
Only one human HIV vaccine has shown any level of protective efficacy. However the mechanisms behind how this vaccine was protective are still not fully understood. Additionally, HIV is primarily transmitted through mucosal sites, however very little is know about vaccine immune responses at these sites. Thus this proposal aims to further define the mechanisms of antibody protection against HIV at both systemic and mucosal locations, in order to guide future HIV vaccine design efforts.
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.
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.