Mimetics Of Natural Triggers Of Innate Immunity As Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. ....Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. There is very little known about how adjuvants actually work but many of the highly effective experimental adjuvants contain an immunostimulant which is usually either whole dead bacteria or components of the cell walls of bacteria or other organisms. From evidence emerging in the literature and our own experimental observations, we have begun to understand the requirements for and the chain of events leading to immune response induction. The interaction of certain lipid-containing groups, present on antigens from pathogenic organisms, with a specialised type of cell, the dendritic cell, is a key event in this process. We have designed synthetic mimics of lipid-containing moieties from bacteria and coupled them to unrelated parts of viral proteins. We showed that these lipopeptides can elicit potent anti-viral immune responses and long lived memory responses. The experiments outlined in this proposal will examine the interaction of these and other second generation lipopeptides with dendritic cells. We will determine whether these can bind to particular molecules on the dendritic cell surface to initiate a specific series of signals leading to immune induction and if so we will seek to use different lipid groups to trigger the immune response in different and predictable ways. The outcomes of this work may have a major impact on the design of new vaccines as well as increase our understanding of how the immune system is triggered to respond to invading organisms.Read moreRead less
A Double Blind Randomised Placebo Controlled Trial Of Melatonin As An Adjuvant Agent In Induction Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$384,566.00
Summary
Induction of labour, a common obstetric intervention fails in almost 40% of first time mothers. There is evidence to suggest that the endogenous hormone melatonin has important roles in the progress of labour. We will undertake a double-blind randomised placebo controlled trial of melatonin supplementation to improve the success of induction of labour in first time mothers. We will also assess the economic impact of melatonin supplementation at induction of labour.
Lymph Node Stromal Cells: Phenotype, Function And The Induction Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$340,550.00
Summary
Autoimmune diseases, where the immune system kills our own tissue, are initiated in lymph nodes. Lymph node structural cells, called fibroblastic reticular cells (FRC), kill white blood cells capable of reacting against the body's own proteins. FRC could be used to prevent diseases like type I diabetes, but little is understood about their actions. We propose to study the way they work and their potential to prevent or treat autoimmunity when transplanted in mice.