The Use Of Inulin-based Adjuvants To Enhance The Effectiveness And Population Coverage Of Influenza Vaccination
Funder
National Health and Medical Research Council
Funding Amount
$250,393.00
Summary
A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This tec ....A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This technology is known as a vaccine adjuvant and we have developed a unique adjuvant based on a natural plant sugar called inulin that has the potential to dramatically enhance existing and new flu vaccines.Read moreRead less
Mechanism of action of an anti-inflammatory compound which targets alternatively activated macrophages. The project will study the mechanism by which a novel anti-inflammatory compound, developed by our commercial partner, suppresses the activity of a population of cells known as alternatively activated macrophages. These cells play a key role in driving allergic inflammation, including the inflammation associated with asthma.
The Early Inflammatory Response To Virulent And Avirulent Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells s ....Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells such as macrophages. By avoiding this route of uptake and destruction, the virus is free to infect and replicate in other cells of the respiratory tract. Furthermore, by evading macrophage entry, the virus avoids triggering the release of early inflammatory mediators from these cells and this may affect both the speed and the magnitude of the subsequent inflammatory response. This study will contribute to a greater understanding of factors involved in initiating and regulating inflammation in the respiratory tract following viral infection. Furthermore, the findings may provide new insights into mechanisms of virulence of influenza and other enveloped viruses.Read moreRead less
Development of microbial bioproducts for the suppression of inflammation. Asthma and inflammatory diseases are serious health problems that result from excessive inflammation. Exposure to bacteria may reduce inflammation. This project will identify the bacterial components that reduce inflammation and develop them into new anti-inflammatory therapies for asthma.
Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test ....Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test the effect of pharmacological inhibition of established molecules such as RIPK2 or IAPs in NOD dependent models for human diseases. Outcomes of this study will be of the utmost interest for the treatment of NOD driven diseases such as Crohn's disease, Blau syndrome or asthma.Read moreRead less
A new approach to reversing and preventing immune-mediated diseases. Chronic inflammatory diseases affect up to 20 per cent of Australians. These diseases reduce wellbeing and life potential and shorten lifespan. This project addresses the urgent need for effective therapies and focuses on developing strategies for disease cure and prevention.
Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection follo ....Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection following a single administration. The aims of this study are to investigate the immunological mechanisms underlying the protective response by this novel vaccine using bovine and murine models. This study will discover new control measures for botulism in Australia.Read moreRead less
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
Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM re ....Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM remodelling. Previous studies have developed a unique mouse model of childhood asthma and discovered the molecular mechanism by which this tissue tropism develops in response to virus infection. This project will identify new targets for immunomodulation and design new biologics to block ASM remodelling and the deleterious effects of respiratory virus infection in asthmatic subjects. Read moreRead less
Investigation of the immunological properties of a novel adjuvant in sheep. The induction of strong immune responses without side effects is a highly desirable goal in vaccine R&D. The recently developed adjuvant DCtag utilises unique properties of dendritic cells to boost both cellular and humoral immune responses without tissue damage. This project will identify the mechanisms of immune induction of DCtag using unique properties of our sheep cannulation model. This will allow further optimisat ....Investigation of the immunological properties of a novel adjuvant in sheep. The induction of strong immune responses without side effects is a highly desirable goal in vaccine R&D. The recently developed adjuvant DCtag utilises unique properties of dendritic cells to boost both cellular and humoral immune responses without tissue damage. This project will identify the mechanisms of immune induction of DCtag using unique properties of our sheep cannulation model. This will allow further optimisation of DCtag adjuvanticity in sheep, which will then be applied to the delivery of a prototype peptide based vaccine against foot and mouth disease virus, a veterinary disease of global importance, hereby increasing Australia's leadership in biotechnology.Read moreRead less