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The Adaptive Immune Response To Epstein-Barr Virus.
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against ....Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against EBV.Read moreRead less
Improving and manipulating the immune adjuvant properties of recombinant fowlpox vectors. Unbalanced immune responses may cause or worsen common and important diseases such as infections, allergies, cancers and autoimmunity. Interleukin-4 (IL-4) is the only immune active product or cytokine that safely skews an aberrant immune response to a healing type of response. Fowlpox viruses (FPV) provide safe and effective human vaccines. Engineering FPV to make both a relevant antigen and a cytokine is ....Improving and manipulating the immune adjuvant properties of recombinant fowlpox vectors. Unbalanced immune responses may cause or worsen common and important diseases such as infections, allergies, cancers and autoimmunity. Interleukin-4 (IL-4) is the only immune active product or cytokine that safely skews an aberrant immune response to a healing type of response. Fowlpox viruses (FPV) provide safe and effective human vaccines. Engineering FPV to make both a relevant antigen and a cytokine is proprietary technology. With our commercial partner and using experimental mice, we will test the concept that FPV making a model antigen and IL-4 initiate and/or maintain beneficial Type 2 responses. A successful outcome will guide clinical FPV-based vaccine development for the treatment of important human and veterinary diseases.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
Molecular determinants of an allergic response. Some humans develop allergies after exposure to environmental allergens while others do not. At present, the reason for this individual variation is not known. By comparing the processes activated in allergic versus non-allergic individuals, this study will identify critical molecules involved in making individuals susceptible to allergies, which will be used to develop safer and more effective allergy vaccines.
Understanding The Mechanisms Of Action Of The ISCOMATRIX Adjuvant For The Development Of Human Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
CSL Limited, an Australian owned global biopharmaceutical company, is developing the ISCOMATRIX (IMX) adjuvant for vaccines to prevent and treat serious human disease of global concern (e.g. cancer, pandemic flu, HPV, HCV). This study will identify the mechanisms of action of IMX in generating strong cellular immunity, how to enhance it further by combining with other immuno-modulators so as to develop novel IMX vaccines for the treatment of established cancer and persistent viral infections.
Role Of PLZF In Regulating The Interferon Response
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The Interferon (IFN) pathway is essential for immune defense against pathogens in vertebrates. IFNs both protect and alert cells about viral, bacterial, and other immune assaults and promote a cellular antiviral state, reduce proliferation, or induce apoptosis depending on the cell type and environment. Based on these properties, IFNs have been used clinically against a variety of diseases including viral infections, immunomodulatory disorders and hematologic and solid tumors including renal cel ....The Interferon (IFN) pathway is essential for immune defense against pathogens in vertebrates. IFNs both protect and alert cells about viral, bacterial, and other immune assaults and promote a cellular antiviral state, reduce proliferation, or induce apoptosis depending on the cell type and environment. Based on these properties, IFNs have been used clinically against a variety of diseases including viral infections, immunomodulatory disorders and hematologic and solid tumors including renal cell carcinoma. However, the factors determining outcome of IFN treatment, remain to be determined. We have identified a subset of interferon stimulated genes whose sustained expression was found to correlate with heightened antiviral sensitivity of renal cell carcinoma cell lines to IFN. Many of these genes were found to have binding sites for the transcriptional repressor promyleocytic zinc finger protein (PLZF). PLZF was first identified in a subset of Acute Promyelocytic Leukemia patients and is involved in maintenance of erythroid lineage stem cells and spermatogonial stem cells in male mice. PLZF has not previously been implicated in the IFN response. Accordingly, we investigated the expression of interferon stimulated genes and showed that increased expression of immune related genes depends on PLZF expression. PLZF was also found to directly associate with binding sites in promoters of interferon stimulated genes and that this requires histone deacetylation. Thus, we uncovered a novel function for PLZF in enhancement of IFN associated gene expression. We propose to test the hypothesis that PLZF is an essential component of the IFN response. As a corollary, we will also test whether PLZF expression can be linked to IFN responsiveness in renal cell carcinoma. These studies will establish the role of PLZF in the IFN response and define its utility in predicting IFN responsiveness in therapeutic applications.Read moreRead less
Human Dendritic Cell Subsets And Their Application For Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
Immunotherapy is a promising non-toxic strategy for the treatment of many cancers, viruses and other diseases. It works by teaching the patient's own immune system to recognize and destroy the cancer. Specialized blood cells called dendritic cells are essential to this process but they are poorly understood in humans. I aim to investigate the function these cells and use this information to develop new treatments for cancer and viruses.
Investigation of the resilience of immune memory to manipulation by pathogens. Vaccines have a major impact on the wellbeing of humans as well as productivity and welfare of veterinary species and pets. New vaccines have therefore a tremendous effect on both the economy and the community. Here we investigate in how far an adjuvanted vaccine can influence the type of immune response induced during subsequent infection when the pathogen has developed mechanisms to subvert the induced protective im ....Investigation of the resilience of immune memory to manipulation by pathogens. Vaccines have a major impact on the wellbeing of humans as well as productivity and welfare of veterinary species and pets. New vaccines have therefore a tremendous effect on both the economy and the community. Here we investigate in how far an adjuvanted vaccine can influence the type of immune response induced during subsequent infection when the pathogen has developed mechanisms to subvert the induced protective immune response. This question has profound implications for all vaccine and adjuvant development activities, as the resilience of immune memory is not yet considered an important parameter in the design of adjuvants yet it is fundamental to the successful of vaccines against many pathogens.Read moreRead less