Using Influenza Vaccination To Understand And Improve Anti-viral Immunity In COPD
Funder
National Health and Medical Research Council
Funding Amount
$1,316,597.00
Summary
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. Lung infections often make those afflicted by COPD very unwell. We have recently shown that influenza vaccination induces a poor antibody response in many COPD patients. This study will examine why this is the case, and what can be done to restore normal immune function. In the final year of the Project, we will assess whether doubling the dose of influenza vaccination is helpful.
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that result in the generation of mucosal memory T cells that are resistant to virus infection.
Role Of The CD8-Heparan Sulfate Interaction In CD8+ T Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$649,135.00
Summary
The immune system can recognise a large array of foreign pathogens without reacting to self-components. For this to occur T cells, the main mediators of immunity, must be made to tolerate self-molecules as they develop in the thymus. We have identified a novel interaction between a molecule called CD8 on T cells and a complex carbohydrate called heparan-sulfate, which helps auto-reactive T cells to be eliminates in the thymus. The aim of this project is to further investigate this phenomenon.
Multiple Paths Of TFH Differentiation And Their Impact On B Cell Protection Against Infection
Funder
National Health and Medical Research Council
Funding Amount
$923,466.00
Summary
Collaboration between T and B cells is crucial for immune protection and underpins current vaccine strategies. We have revealed an unappreciated flexibility that exists in T cell responses which varies the instructions they give B cells. It is likely this tailors immune responses to ensure protection to countless infectious diseases. This project uses cutting-edge technologies to understand this flexibility and has important implications for vaccine design and treatment of infectious disease.
An Investigation Into The Adaptive Immune Response In Celiac Disease
Funder
National Health and Medical Research Council
Funding Amount
$597,167.00
Summary
Celiac Disease (CD), an autoimmune-like disease that is triggered by the ingestion of dietary wheat gluten, or related proteins from rye and barely, affects ~1% of the population, causing tissue damage in the small intestine. The only available treatment is strict adherence to a lifelong gluten free diet. Our project aims to understand, at the molecular level, how components of the immune system and gluten interact to trigger the immune response that leads to CD symptoms.
We will construct different genetically engineered viruses, which infect cells in the respiratory tract, to deliver genes encoding proteins from human immunodeficiency virus (the AIDS virus). These engineered viruses can be expected to generate an active immune response in mucosal tissues, including the vaginal and rectal tracts. As these are the major routes for transmission of the AIDS virus, these new vaccines are expected to reduce transmission of the AIDS virus.
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.
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
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.