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
Production Of A Novel Humanised Anti Dendritic Cell Therapeutic Antibody For Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$202,500.00
Summary
A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be use ....A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be useful for the prevention of rejection in solid organ transplantation. If successful, it will selectively control graft versus host disease, without compromising the essential anti-viral immunity and desired anti-leukemia activity of the graft.Read moreRead less
Identifying Molecular Machinery In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$687,500.00
Summary
Vaccines invoke immune responses that will protect a vaccinated host if they encounter infection. Vaccines can also be deployed to fight cancer. 'Dendritic cells' are the key immune cell responsible for vaccine immunity. While dendritic cells are pivotal to initiating vaccination, little is known about their internal machinery. This research proposal will identify new machinery for dendritic cell vaccine immunity that will serve as therapeutic targets to boost vaccination.
Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to th ....Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to the immune system. We have already identified some proteins that are expressed on the surface of only one type of dendritic cell. We will explore the possible use of these proteins as a means of delivering a vaccine to only one type of dendritic cell. This project will also identify new genes that are expressed in some types of dendritic cells but not others. These new genes whose expression does differ amongst the dendritic cells are potential targets for manipulating the immune system and ensuring more efficient vaccination.Read moreRead less
The Role Of The Dendritic Cell Surface Molecule Clec9A In Dendritic Cell Subset Function And Dead Cell Recognition
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Dendritic cells (DC) are sentinels of the immune system. DC monitor the environment and regulate tolerance to self versus immunity to dangerous material. Different types of DC perform different jobs. We have identified a new surface molecule, Clec9A, on some mouse and human DC. We will investigate the function of Clec9A in the immune response. We will also use Clec9A to help unite mouse and human DC biology, since until now there have been few useful marker molecules common to both species.
Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. The ....Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. These cells (dendritic cells) are genetically modified to express the molecular targets of the autoimmune response. This in turn switches off the response to these targets. In this project, we will explore how these cells can be used to turn off the harmful cells present in the immune system.Read moreRead less
Role Of Dendritic Cell Subsets In The Generation Of CD4 T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$563,554.00
Summary
This project studies the mechanisms responsible for establishing immunologic memory that is generated by vaccination and determines its efficacy. We aim to identify and study previously unacknowledged factors that critically affect the efficacy of vaccination. The results will be significant for both preventative and therapeutic vaccination (cancer, autoimmunity) and will help us to design new vaccines to improve immune function in infection, autoimmunity and cancer.
Dissecting The Contribution Of CD103+ DC To Priming Of Virus-specific CD8 T Cells
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Dendritic cells are key regulators of T cell responses against pathogens. This project will examine the contribution and individual function of distinct dendritic cell to the initiation of adaptive immune responses against herpes-simplex virus. Unraveling the delicate interplay between different dendritic cells will provide novel insights into host-pathogen interactions and will have important implications for the development of efficient vaccination strategies.