Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifyin ....Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifying how they are formed and how they behave within the body. This work will therefore contribute to the development and production of new-generation vaccines to these so far uncontrollable infectious diseases.Read moreRead less
Understanding the dynamics of T cell responses to chronic infection. The health, social, and economic impact of chronic infections on the Australian and global populations is enormous. A major obstacle to the development of vaccines against chronic infections is that we have a poor understanding of immune responses to persistent infections. We aim to use bioinformatics and mathematical modelling to understand immune responses to persistent viruses so that we can improve the long-term immune cont ....Understanding the dynamics of T cell responses to chronic infection. The health, social, and economic impact of chronic infections on the Australian and global populations is enormous. A major obstacle to the development of vaccines against chronic infections is that we have a poor understanding of immune responses to persistent infections. We aim to use bioinformatics and mathematical modelling to understand immune responses to persistent viruses so that we can improve the long-term immune control of chronic viral infections such as the human immunodeficiency virus (HIV). This project will strengthen Australian research in the area of interdisciplinary approaches to immunology, which is becoming crucial to interpreting the rapidly increasing volume of data obtained using advanced experimental techniques.Read moreRead less
T cell recognition and control of virus: the balance between T cell receptor diversity and degeneracy. T cells provide an important line of defence in the immune system's resistance against infectious diseases. However, changes to the T cell population during prolonged infection, and with age, can compromise the immune system's ability to fight effectively viral infections. The proposed research will greatly improve our understanding of the recognition and control of viral infections by T cells. ....T cell recognition and control of virus: the balance between T cell receptor diversity and degeneracy. T cells provide an important line of defence in the immune system's resistance against infectious diseases. However, changes to the T cell population during prolonged infection, and with age, can compromise the immune system's ability to fight effectively viral infections. The proposed research will greatly improve our understanding of the recognition and control of viral infections by T cells. The insights gained from this research will enable us to exploit key features of T cell responses to improve the outcome of viral infections in elderly individuals and to develop better vaccines for protection against a range of infectious diseases that affect the Australian population, including HIV and Hepatitis C.Read moreRead less
Development of an effective vaccine for chlamydial infection: optimisation of a non-toxic cholera toxin-based adjuvant to generate a protective mucosal response. Chlamydial genital infections are the most common sexually transmitted infection in Australia and the world and impose a major health burden on the community. Chlamydial infections are also associated with cardiovascular disease, Australia's biggest killer and asthma, another condition that has increased significantly in prevalence in t ....Development of an effective vaccine for chlamydial infection: optimisation of a non-toxic cholera toxin-based adjuvant to generate a protective mucosal response. Chlamydial genital infections are the most common sexually transmitted infection in Australia and the world and impose a major health burden on the community. Chlamydial infections are also associated with cardiovascular disease, Australia's biggest killer and asthma, another condition that has increased significantly in prevalence in the past 10 years. This project will evaluate the effectiveness of a new adjuvant as a first step towards the development of a vaccine to target these important infections.Read moreRead less
Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is ....Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is generated in the immune response, and how it becomes narrowed with age or prolonged infection. This information can be used to design vaccines for persistent infections such as HIV, and to improve immune control of infection in the elderly.Read moreRead less
Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow u ....Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow us to develop LipoVax as a new platform technology that can be applied to the development of human vaccines, veterinary vaccines, vaccines for companion animals and vaccines to target infections in feral animals and native wildlife population populations.Read moreRead less
Foreign DNA is a danger signal for mammalian cells. This project investigates how cells normally respond to foreign DNA, and is relevant to understanding how the body fights infections, particularly by viruses. The results will help us to design more effective treatments for infectious disease. Studying responses to DNA will also promote the design of new treatments for the autoimmune disease lupus, and help improve technologies or treatments where DNA is introduced into cells or tissues. This ....Foreign DNA is a danger signal for mammalian cells. This project investigates how cells normally respond to foreign DNA, and is relevant to understanding how the body fights infections, particularly by viruses. The results will help us to design more effective treatments for infectious disease. Studying responses to DNA will also promote the design of new treatments for the autoimmune disease lupus, and help improve technologies or treatments where DNA is introduced into cells or tissues. This includes gene therapy, new strategies for vaccination, and the production of proteins as drugs by biotechnology. The project will promote National Research Priorities in the areas of preventative healthcare, ageing well ageing productively, breakthrough science and new technologies.Read moreRead less
Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and w ....Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and will create new knowledge and resources to improve human and animal health through vaccines, pharmaceuticals and public health policy. 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
Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gat ....Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gathered much information about such epitopes, recent studies have shown that some unexpected regions of pathogens are targets for killer T cells. This project will break new ground by utilising unbiased procedures to assess the relative contribution of these noncanonical epitopes to immunity.Read moreRead less