Development Of Novel Vaccine Strategies To Prevent Genital Tract Chlamydial Infection
Funder
National Health and Medical Research Council
Funding Amount
$408,556.00
Summary
Genital tract chlamydial infection is the most common bacterial sexually transmitted disease world wide with 4-5 million cases occurring annually throughout the world. The incidence of chlamydial infection is increasing in the Australian population. The majority of infections in women are asymptomatic and, if untreated, go on to cause pelvic inflammatory disease, ectopic pregnancy and infertility. These conditions can be life threatening and are a significant public health cost. In the proposal ....Genital tract chlamydial infection is the most common bacterial sexually transmitted disease world wide with 4-5 million cases occurring annually throughout the world. The incidence of chlamydial infection is increasing in the Australian population. The majority of infections in women are asymptomatic and, if untreated, go on to cause pelvic inflammatory disease, ectopic pregnancy and infertility. These conditions can be life threatening and are a significant public health cost. In the proposal we will develop novel vaccine strategies, involving both intranasal immunisation and immunisation by direct application to the skin, to induce protection against genital tract chlamydial infection. These studies will lay the basis for human trials of a vaccine to prevent what is now the most common STD in Australia. Such a vaccine to target this chronic infection would represent a major advance in preventive healthcare for the maintenance of good health.Read moreRead less
Immunodominance In Vaccinia Virus And Recombinant Vaccinia Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$388,455.00
Summary
When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do ....When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do not understand well, T cells that recognize only a few out of the many peptides will dominate an entire immune response. As a result, immune responses are focused in such a way that they recognize only a tiny portion of an invading microbe. Focusing of immune responses also occurs during immunization with vaccines. Some new, genetically engineered vaccines use a harmless microbe to carry small parts of more dangerous pathogens. The parts chosen will not cause any disease by themselves, so the whole vaccine is safe. Vaccines built in this way are in clinical trials for diseases such as AIDS and malaria, but do not work as well as was hoped. These new vaccines are largely made up of the carrier and the parts of the microbe we wish to immunize against (e.g. a part of the AIDS virus) will be only a small fraction of the whole vaccine. Ideally we would like the immune system to focus on this small part of our choosing, but the few studies done suggest that this is not the case. In this project we will study vaccines that use a carrier called vaccinia virus. We will test to what extent immune responses are focused inappropriately. We will then genetically alter the virus and use new immunisation strategies to try and shift the focus of the immune response so that it targets the right parts of the vaccine. The ultimate aim is to improve vaccines, but in the process we may learn more about how the immune system chooses its targets.Read moreRead less
The Role Of Secretory Antibodies In Mucosal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of th ....This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of the mucosal tissues, to prevent recognition of this material by the immune system. Such recognition could result in serious consequences both locally (ie. in the gut) and more distally eg. in the pnacreas leading to diabetes. As a consequence, we believe that these antibodies are fundamental to health. The research could have important ramifications for diseases resulting from immune responses against host tissues, so-called autoimmune diseases like diabetes.Read moreRead less
Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restricti ....Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restriction). T lymphocytes that can recognise antigens in the absence of MHC or MHC like molecules challenges a major paradigm in the field of immunology. As T cell based therapy underpins treatments for cancer and infection, new mechanisms of T cell activation that are independent of patient genotype should ultimately create opportunities for therapeutic and commercial development, leading to both health and economic benefits.Read moreRead less
CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to ....CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to these lipids; 2. The cellular receptors that bind to these lipids; 3. The types of lipids involved in this process. This work is essential for us to understand lipid-based immunology which is critical if we ultimately wish to harness this to improve human health.Read moreRead less
Understanding immune mechanisms induced by pulmonary vaccination. This project aims to better understand the mechanisms of immune induction of a novel lung vaccination strategy. The ability to deliver vaccines that induce potent lung and body wide immune responses in a safe and efficient manner has wide implications for both human and animal health. Ultimately, the vaccine will be delivered to the lung as stable dry powders in an attempt to negate the need for a transport cold chain and therefor ....Understanding immune mechanisms induced by pulmonary vaccination. This project aims to better understand the mechanisms of immune induction of a novel lung vaccination strategy. The ability to deliver vaccines that induce potent lung and body wide immune responses in a safe and efficient manner has wide implications for both human and animal health. Ultimately, the vaccine will be delivered to the lung as stable dry powders in an attempt to negate the need for a transport cold chain and therefore facilitate the distribution of the vaccines to remote areas. The project will not only benefit the Australian biotechnology industry but also the community at large and in particular those in remote areas without access to modern medical facilities.Read moreRead less
Defining the microenvironmental regulators of spleen function and immunity. The spleen is an important organ that is present in almost all vertebrates and is a critical site for the induction of systemic immune responses. The current paradigms of spleen biology are mostly derived from rodent studies, but the cellular biology of the spleen in humans remains poorly defined. Using novel tools, advanced transcriptomics and imaging techniques this project aims to reveal the functions of stromal cells ....Defining the microenvironmental regulators of spleen function and immunity. The spleen is an important organ that is present in almost all vertebrates and is a critical site for the induction of systemic immune responses. The current paradigms of spleen biology are mostly derived from rodent studies, but the cellular biology of the spleen in humans remains poorly defined. Using novel tools, advanced transcriptomics and imaging techniques this project aims to reveal the functions of stromal cells in the spleen in humans and to define the fundamental roles of spleen stromal cells in long-lived immunity. The anticipated outcomes are to build Australia’s research capacity and to generate new knowledge of significance for our fundamental understanding of the spleen and the role of this tissue in the immune system.Read moreRead less
Understanding T cell immunity induced by infection. We aim to understand how killer T cells are “programmed” upon activation and acquire their characteristic functions and how these are maintained into immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.
Butyrophilin ligand sensing by the immune system. T cells are an important part of the immune system, surveying our body and preventing many diseases. A subset of T cells, gamma delta T cells, are a crucial component of the immune system. A key problem is that the mechanism(s) controlling gamma delta T cell behaviour are poorly understood. This proposal aims to decode how these cells are triggered into action by using innovative tools to investigate the molecular basis underpinning their functio ....Butyrophilin ligand sensing by the immune system. T cells are an important part of the immune system, surveying our body and preventing many diseases. A subset of T cells, gamma delta T cells, are a crucial component of the immune system. A key problem is that the mechanism(s) controlling gamma delta T cell behaviour are poorly understood. This proposal aims to decode how these cells are triggered into action by using innovative tools to investigate the molecular basis underpinning their function. This project expects to create fundamental new knowledge regarding how gamma-delta T cells are regulated, which will ultimately allow us to harness these cells to improve health.Read moreRead less