Using The Information Inherent In Immune Responses To Design Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$526,571.00
Summary
The parts of viruses, bacteria and of cancer cells that are recognised by the immune system are called epitopes. Epitopes are generated from these agents by dendritic cells which are found in many parts of the body where they act as sentinels on the look out for dangerous organisms. Epitopes are very small pieces of the proteins against which immune responses are mounted and can be readily synthesised in the laboratory. If we were to design vaccines that are made of epitopes such that the immune ....The parts of viruses, bacteria and of cancer cells that are recognised by the immune system are called epitopes. Epitopes are generated from these agents by dendritic cells which are found in many parts of the body where they act as sentinels on the look out for dangerous organisms. Epitopes are very small pieces of the proteins against which immune responses are mounted and can be readily synthesised in the laboratory. If we were to design vaccines that are made of epitopes such that the immune response is focussed to those exact regions of infectious agents it could lead to an immune response that eliminates the agent. The problem is, however, that we usually do not know which part of the virus, bacterium or cancer cell is recognised as an epitope. So the identification of epitopes is a limitation to the design of epitope-based vaccines. Anyone who has encountered a virus, bacterium or tumour cell and who has raised an immune response will have developed antibodies and immune cells able to recognise the right parts of the infectious agent or cancer cell. These antibodies and immune cells now contain information about the epitopes. We will use antibodies and blood cells obtained from people immune to the disease to extract epitopes from a panel of protein fragments that represent the agent against which we wish to make vaccines. These newly discovered epitopes will then be incorporated into totally synthetic vaccines. These vaccines will also incorporate a simple lipid molecule which specifically targets and activates the dendritic cell that is key for the induction of potent immune responses. All of the technologies we propose are in place and we have proof of principle that the approach leads to the successful design of vaccines that are effective against infectious diseases and cancers.Read moreRead less
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
Targeting Polymyxin-resistant Gram-negative Superbugs: Development Of Novel Antimicrobial Lipopeptides
Funder
National Health and Medical Research Council
Funding Amount
$661,069.00
Summary
Prevalence of resistance to antibiotics among Gram-negative 'superbugs' is a major global medical challenge, which is highlighted by the Bad Bugs, No Drugs campaign of the Infectious Diseases Society of America. There are virtually no new antibiotics in the current drug development pipeline for these dangerous pathogens. In this project, novel lipopeptides will be designed, synthesised and evaluated against these 'superbugs'. Information obtained will be crucial for further drug development.
Modelling and Performance Evaluation of Stab and Ballistic Resistant Fabrics. The aims of the project are to model and design stab resistant fabrics, and evaluate their stab and ballistic performance under simulated end-use conditions. Bi-component ballistic and stab resistant wearable and concealable garments will be produced and comprehensively characterised. This program is a significant first step towards developing Australian owned intellectual property for specialised protective garments f ....Modelling and Performance Evaluation of Stab and Ballistic Resistant Fabrics. The aims of the project are to model and design stab resistant fabrics, and evaluate their stab and ballistic performance under simulated end-use conditions. Bi-component ballistic and stab resistant wearable and concealable garments will be produced and comprehensively characterised. This program is a significant first step towards developing Australian owned intellectual property for specialised protective garments for local and export markets. Results from this study will produce fundamental knowledge on stab and ballistic resistant fabrics and armours, and provide practical information on the preparation of commercially acceptable protective products.Read moreRead less