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We have discovered how a rare type of human antibody called IgG4 exerts a major regulatory influence on the body's immune system. We have discovered how IgG4 can "switch" off inflammatory white blood cells which has broad implications for the development of new forms of therapy for switching off allergies and autoimmune diseases and for switching on immunity to infections and cancers.
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.
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.
Dissecting Human B-cell Function: From Primary Immunodeficiencies To Chronic Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Despite knowing a lot about immunity in a mice, functional analysis of the human immune system has been a major challenge. I will study defects of immune cells in humans with gene mutations that cause an antibody deficiency. With new insights from these unique clinical samples, I will functionally dissect human immune responses, directly translate these to chronic inflammatory disease, and provide implications for future vaccine development and cancer treatment.
Chronic infectious diseases have a devastating effect on global health. HIV and Plasmodium falciparum both cause chronic disease and have evaded effective vaccine design. Vaccines rely on immune memory – the ability to clear an infection rapidly to a previously encountered pathogen. This proposal investigates the formation and dysfunction of immune memory in chronic infectious diseases, which will be vital for creating new and effective vaccines.
This Program Grant brings together a world-leading team of experts to elucidate mechanisms that protect most people from infection by making antibodies, and their failure caused by genes or infections like influenza or HIV. The team will determine mechanisms that protect most people from making antibodies against normal parts of our body, whose failure causes numerous autoimmune diseases including rheumatoid arthritis. The team will develop ways to engineer better antibodies.
Dissecting The Mechanisms Of Vaccine Immunogenicity And Induction Of Protective Immunity Against Influenza Virus
Funder
National Health and Medical Research Council
Funding Amount
$365,145.00
Summary
Influenza pandemics have historically led to worldwide morbidity and mortality. Vaccination remains to be the only plausible strategy to limit widespread mortality as a result of an influenza pandemic. The parts of the immune system important in protecting individuals from influenza virus are poorly understood. This research aims to understand the important correlates of protective immunity in order to improve vaccine design.
Regulation Of The Production Of IgE Antibodies By Antigen-specific B Cells
Funder
National Health and Medical Research Council
Funding Amount
$330,662.00
Summary
Our team has been studying the immune cells that make antibodies and recently discovered that cells without a particular gene make large amounts of IgE antibody. IgE is responsible for asthma and other allergies, which are a major cause of morbidity in the Western world. Based on this discovery, we aim to find out exactly how and why IgE is made in some circumstances but not others, and what other immune cells are involved. These results will identify a way to prevent asthma and other allergies.
This project will assess new ways to protect against HIV infection and treat HIV infection using potent antibody therapies. This will help us understand how the immune system can control HIV. We will generate antibody fragments that can be produced relatively cheaply that, if successful, could lead to a viable antibody therapy for HIV.