VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.
Novel Posttranscriptional Pathways The Control Tfh Cell Numbers
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
T follicular helper (Tfh) cells are essential for effective antibody responses against infection. Limiting Tfh cells is crucial for selecting the "fittest" B cells and the success of vaccines. Tfh cell accumulation causes autoimmuity and is associated with inadequate B cell responses in HIV infection. We have recently discovered two novel pathways that control Tfh cells. We speculate they regulate different RNAs that influence Tfh homeostasis and aim to elucidate their mechanism of action.
In Vivo Imaging Of Protective And Malignant B Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$431,412.00
Summary
B cells are responsible for producing antibody that protects us from infection. Disruption of healthy B cell function can lead to a myriad of diseases including immunodeficiency, autoimmunity and blood cancers such as leukaemia. The aim of my work is to use powerful microscopy to visualise how mutated B cells interact with their surrounding environment in real-time. These studies will allow the development of new treatments for cancer and immune conditions that target these interactions.
Defining The Requirements For Effective Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses ....The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses.Read moreRead less
Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic ....Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic use (e.g. cancer).Read moreRead less
Determining The Unique Processes That Control Memory B Cell-mediated Secondary Antibody Responses
Funder
National Health and Medical Research Council
Funding Amount
$853,644.00
Summary
Vaccines educate the immune system by training memory cells to make neutralizing antibodies when it re-encounters the pathogen. However, where and how these memory cells are activated in the secondary antibody response in immune animals remain unknown. Here we use cutting edge technologies to fate map and gene profile memory cells and determine the molecular switches that control the secondary antibody response. This will be complemented by human vaccine studies.
Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
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.
Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.