Vaccines aim to protect against future infections by inducing memory in the immune system so that the host can react quickly to the next challenge. Defence against viral infections and some cancers depends in part on activating CD8+ T cells, a class of white blood cell that can recognise and kill infected or malignant cells. The ideal vaccines against these challenges would therefore generate high numbers of long-lived CD8+ T cells that are programmed to make the right response if the infection ....Vaccines aim to protect against future infections by inducing memory in the immune system so that the host can react quickly to the next challenge. Defence against viral infections and some cancers depends in part on activating CD8+ T cells, a class of white blood cell that can recognise and kill infected or malignant cells. The ideal vaccines against these challenges would therefore generate high numbers of long-lived CD8+ T cells that are programmed to make the right response if the infection or tumour re-emerges. Little is known about the programming of memory CD8+ T cells. We have recently found that some of these cells have the potential to be reprogrammed to display different functions by exposure to new stimuli. This opens up the possibility that ineffective responses could be improved by using vaccination to control the production of these flexible or multipotential memory cells or to reprogram them once they are formed. Alternatively, effective responses might be subverted by pathogens to the detriment of the host. The goal of this project is to learn how the first exposure to an immune challenge influences the development of these multipotential memory CD8+ cells. Understanding the signals and processes that generate multipotential memory cells will be the first step towards developing ways to manipulate them to improve immune defence.Read moreRead less
Population Dynamics Of Tissue-specific Effector And Regulatory CD4+ T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,250.00
Summary
Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. Fro ....Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. From our previous studies of autoimmune gastritis we have generated cell lines of lymphocytes that recognise stomach-specific antigens and with these unique reagents we will perform experiments to determine the fate of these self-reactive T cells in a normal individual. Also we will determine the impact of different amounts of the tissue antigens on the survival and activation of self-reactive T cells, and finally how a special class of lymphocytes, know as regulatory lymphocytes, act in vivo to control the activity of self-reactive T cells. We will use not only classical immunological approaches to address these issues but also state of the art imaging, to visualise the nature of the cell interactions in living tissues. The information arising from this work will underpin strategies to selectively turn off self-reactive lymphocytes that cause disease, will form the basis of clinical development of cell based therapies to treat autoimmune diseases, and the imaging technologies developed in this grant will have wide applicability to the study of a range of immune responses.Read moreRead less
Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently ....Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently restrained by the difficulty of breaking immunological tolerance. We envisage the construction of a anti-cancer vaccine vector with obvious market potential. An exciting prospect is that this approach could be used as a prophylactic vaccine and possibly also as a therapeutic vaccine.Read moreRead less