Characterisation and development of adjuvants for new generation veterinary and human vaccines. Vaccination is the most successful and cost-effective means of combating infectious diseases in both veterinary and human medicine. This project will increase our understanding of how vaccines work and will help the development of new vaccines against infections in both animals and man. The results of these studies will also increase the competitiveness of Australian scientists in the field of vaccine ....Characterisation and development of adjuvants for new generation veterinary and human vaccines. Vaccination is the most successful and cost-effective means of combating infectious diseases in both veterinary and human medicine. This project will increase our understanding of how vaccines work and will help the development of new vaccines against infections in both animals and man. The results of these studies will also increase the competitiveness of Australian scientists in the field of vaccine research and development.Read moreRead less
Equine rhinitis A virus; molecular pathogenesis and methods for control. The horse industry in Australia is primarily based in rural locations and is a major contributor to the national economy both in terms of direct economic contribution to gross domestic product and as a major employer of people in regional Australia. The research proposed in this project will improve our understanding of the pathogenesis of a virus that causes respiratory disease in horses that is related to the virus that c ....Equine rhinitis A virus; molecular pathogenesis and methods for control. The horse industry in Australia is primarily based in rural locations and is a major contributor to the national economy both in terms of direct economic contribution to gross domestic product and as a major employer of people in regional Australia. The research proposed in this project will improve our understanding of the pathogenesis of a virus that causes respiratory disease in horses that is related to the virus that causes foot and mouth disease in ruminants and swine. The technology developed during this project would have a global market.Read moreRead less
Biology Of The Novel C-type Lectin Receptor DCL-1 In Innate And Adaptive Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
The innate immune system is the first line of defense in protecting the body from infection. Phagocytic (meaning eating) white blood cells, which include dendritic cells and macrophages are equipped with cell surface proteins These bind the many types of microbes that cause infection, allowing the phagocytes to destroy them (innate immune response). Furthermore, dendritic cells and macrophages have mechanisms to activate additional specific responses (adaptive immune response) mediated by lympho ....The innate immune system is the first line of defense in protecting the body from infection. Phagocytic (meaning eating) white blood cells, which include dendritic cells and macrophages are equipped with cell surface proteins These bind the many types of microbes that cause infection, allowing the phagocytes to destroy them (innate immune response). Furthermore, dendritic cells and macrophages have mechanisms to activate additional specific responses (adaptive immune response) mediated by lymphocytes (T and B cells). We have discovered a cell surface protein, termed DCL-1, which may play a role in uptake of microbes by phagocytes and activation of innate and adaptive immune responses. This project will examine the mechanisms whereby DCL-1 mediates these immune responses. Understanding the mechanism may allow us to exploit DCL-1 for tumor immunotherapy.Read moreRead less
Role Of Plasmacytoid Dendritic Cells And Neutrophils In The Generation Of Antiviral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
Work described in this application is important in understanding how two very different types of white blood cells, namely neutrophils and plasmacytoid dendritic cells (PDC), contribute to the generation of an effective immune response and control of virus growth. Both these cell types are activated in the earliest phase of the host response and are likely to play crucial roles in determining the nature of the later components of the response. We have recently shown that animals depleted of Gr-1 ....Work described in this application is important in understanding how two very different types of white blood cells, namely neutrophils and plasmacytoid dendritic cells (PDC), contribute to the generation of an effective immune response and control of virus growth. Both these cell types are activated in the earliest phase of the host response and are likely to play crucial roles in determining the nature of the later components of the response. We have recently shown that animals depleted of Gr-1+ cells, with monoclonal antibody (mAb) RB6-8C5, rapidly succumb to a poxvirus infection (mousepox) with 100% mortality. In contrast, mice treated with a control mAb clear the infection very effectively. Host responses essential for recovery from mousepox, including antiviral cytotoxic T lymphocyte (CTL) response and gamma interferon production, are severely diminished in mice treated with the Gr-1+ cell depleting mAb. Since the mAb can potentially deplete both neutrophils and PDC, this raises the important question of whether one or both of these cell types may be involved in the generation of cytokine and cell-mediated immune responses to viral infection. Although PDC and neutrophils themselves are not thought to present antigen to T cells, the elucidation of how they may control the generation of this major arm of the immune response will be novel and has important implications for vaccine design. Virtually nothing is known about how neutrophils or PDC influence viral antigen presentation by antigen presenting cells. Several murine models of viral infection, that in many ways mimic the diseases in humans, will be used to map the sequence of events initiated by PDC and neutrophils and which end in the clearance of virus from the host. Understanding these pathways and identifying the essential mediators and their interactions is critical in elucidating the role of the two cell types in the host response to virus infection.Read moreRead less
Role Of The Natural Killer Complex In The Control Of Murine Malarial Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Natural Killer (NK )cells are an essential arm of the innate immune system. NK cell function is controlled by a series of cell surface receptors encoded within a defined genetic region named the Natural Killer Complex (NKC). This region appears to be highly polymorphic both in mice and humans. It is known that different mouse strains, which differ in the expression of NKC molecules have distinct ability to mount inflammatory responses during infection. In fact, we have previously shown that the ....Natural Killer (NK )cells are an essential arm of the innate immune system. NK cell function is controlled by a series of cell surface receptors encoded within a defined genetic region named the Natural Killer Complex (NKC). This region appears to be highly polymorphic both in mice and humans. It is known that different mouse strains, which differ in the expression of NKC molecules have distinct ability to mount inflammatory responses during infection. In fact, we have previously shown that the differential expression of NKC molecules in mice accounts for the degree of susceptibility to Plasmodium berghei-mediated cerebral malaria, a syndrome that accurately reproduces malarial disease induced by Plasmodium falciparum in humans and that results from an exacerbated pro-inflammatory response to infection. Since the NKC comprises several genes and multi-gene families, the main objective of this proposal is to identify which molecule-s within this genetic region are responsible for the induction of cerebral malaria pathogenesis. Our preliminary results indicate that an activation receptor named Ly49D, which is only expressed on the surface of NK cells from cerebral malaria-susceptible mice, plays a key role in disease-induction. Activation of Ly49D induces NK cells to secrete large amounts of IFN-gamma, a pro-inflammatory cytokine known to mediate cerebral-malaria pathogenesis. We will characterize the immunological function of Ly49D+ NK cells during P. berghei infection and determine whether these cells are the main source of IFN-gamma production. We will also identify the ligand (from parasite or host origin) responsible for the stimulation of this NKC activation receptor during malaria infection. The identification and characterization of these NKC receptors will provide new insights to explain the immunological basis of malarial pathogenesis and could lead to the development of therapeutical approaches designed to prevent severe malarial disease.Read moreRead less
Development of a proto-type vaccine against gastrointestinal nematode larvae. Gastrointestinal parasites are the major cause of production losses in the Australian sheep and wool industries. Drug treatment is predominantly used to control infections but drug resistance has reached critical levels and is threatening the viability of sheep production in many rural areas. In collaboration with an international Animal Health company, we aim to develop vaccines against these parasites and provide a c ....Development of a proto-type vaccine against gastrointestinal nematode larvae. Gastrointestinal parasites are the major cause of production losses in the Australian sheep and wool industries. Drug treatment is predominantly used to control infections but drug resistance has reached critical levels and is threatening the viability of sheep production in many rural areas. In collaboration with an international Animal Health company, we aim to develop vaccines against these parasites and provide a clean, non-toxic alternative to drug treatment. The groundbreaking research involved in this project will also keep Australian animal scientists at the forefront of vaccine research and increase their capacity to attract further support from Industry.Read moreRead less
Development of an anti-Chlamydia vaccine for the koala. The koala is one of Australia's main icons and a major drawcard for tourists. However, it suffers from debilitating disease due to the bacterium Chlamydia, which can lead to severe conjunctivitis, eventual blindness in both sexes, and the females develop untreatable cysts and can become infertile. This project will develop a Chlamydia vaccine to be administered to healthy and diseased koalas in zoos, sanctuaries, koala care centres, relocat ....Development of an anti-Chlamydia vaccine for the koala. The koala is one of Australia's main icons and a major drawcard for tourists. However, it suffers from debilitating disease due to the bacterium Chlamydia, which can lead to severe conjunctivitis, eventual blindness in both sexes, and the females develop untreatable cysts and can become infertile. This project will develop a Chlamydia vaccine to be administered to healthy and diseased koalas in zoos, sanctuaries, koala care centres, relocation programs and eventually perhaps even wild populations. The vaccine findings may also be transferable to other animals and may also even assist the development of a human Chlamydia vaccine.Read moreRead less