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
The In Vivo Biology Of The Novel TGF-b Superfamily Cytokine, MIC-1
Funder
National Health and Medical Research Council
Funding Amount
$280,430.00
Summary
Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important familty of proteins that are involved in wound healing, development and inflammation. Our data thus far suggest thatMIC-1 is an antiinflammatory factor that also involved in reproduction, especially in the health of the placenta. To determine the accuracy of these predictions we wish to use ....Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important familty of proteins that are involved in wound healing, development and inflammation. Our data thus far suggest thatMIC-1 is an antiinflammatory factor that also involved in reproduction, especially in the health of the placenta. To determine the accuracy of these predictions we wish to use genetic techniques to delete this gene from a mouse. Study of this genetically modified mouse will give us a great deal of information on the most important roles of MIC-1.Read moreRead less