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Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Understanding Influenza-specific T Cell Immunity In The Indigenous Population
Funder
National Health and Medical Research Council
Funding Amount
$870,112.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population. There is an urgent need for one-shot universal vaccine that protects against seasonal and pandemic strains. T cells recognising conserved viral regions can elicit such protection. As T cells are restricted by proteins called HLAs, variable between different ethnicities, we will define T cell regions and their HLA restrictions in the Indigenous population to propose strategies for universal T cell-based protecti ....Hospitalisation and death rates from influenza are high in the Indigenous population. There is an urgent need for one-shot universal vaccine that protects against seasonal and pandemic strains. T cells recognising conserved viral regions can elicit such protection. As T cells are restricted by proteins called HLAs, variable between different ethnicities, we will define T cell regions and their HLA restrictions in the Indigenous population to propose strategies for universal T cell-based protective immunity and vaccine design against influenza.Read moreRead less
Intrinsic Host Antiviral Activity Against Pathogenic Filoviruses
Funder
National Health and Medical Research Council
Funding Amount
$488,754.00
Summary
Bats are a major reservoir for deadly human viruses including Ebola and Marburg virus. In contrast to humans, bats can be infected with these viruses without showing clinical signs of disease. The reason why bats can co-exist with these viruses is unknown. This study will determine if a bat antiviral molecule contributes to limiting virus release compared to the human version that could reveal strategies to prevent and control these deadly viruses in humans.
An Inside-out Approach To Muscosal Vaccination: MAdCAM Targeting
Funder
National Health and Medical Research Council
Funding Amount
$174,250.00
Summary
The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the ....The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the gut (called MAdCAM) so that the vaccine is linked to an antibody against MAdCAM. Thus for the first time we believe that a parenteral vaccine ie. injected im or iv (bypassing the oral barriers) can induce mucosal immunity.Read moreRead less
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less
The Centre will enhance Australian clinical immunisation research and training, focussing upon clinical questions with translatable outcomes not easily addressed by industry. Optimal immunisation and interventions to maximise uptake of existing and new vaccines in high risk patient groups, such as children with cancer, immigrants, children with chronic diseases and adolescents will be studied. New vaccine trials, innovative use of existing vaccines, systematic collection of vaccine failure data, ....The Centre will enhance Australian clinical immunisation research and training, focussing upon clinical questions with translatable outcomes not easily addressed by industry. Optimal immunisation and interventions to maximise uptake of existing and new vaccines in high risk patient groups, such as children with cancer, immigrants, children with chronic diseases and adolescents will be studied. New vaccine trials, innovative use of existing vaccines, systematic collection of vaccine failure data, and targeted epidemiology and disease modelling vaccine preventable disease will also allow a broad program of research, enabling training and mentoring of young clinical nurse and physician researchers. Collaborations with existing national immunisation, infectious diseases and research institutions will allow maximal effectiveness of clinical studies.Read moreRead less
Vaccinating Against Helicobacter Pylori-induced Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,088,714.00
Summary
Stomach cancer is the 3rd leading cause of cancer-related deaths. Most stomach cancers result from inflammation due to Helicobacter pylori infection. Most infections are treatable with antibiotics but this does not protect against cancers that develop before infection is diagnosed. Normal vaccine approaches aimed at this infection have been unsuccessful. We have identified a new approach for protecting against stomach cancer by preventing inflammation; this project aims to develop this vaccine.
Generation Of Protective Immunity Against Severe Influenza Disease In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$1,630,970.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population, especially when a new virus emerges. There is an urgent need for a vaccine that protects against all influenza strains. T cells recognising conserved viral regions elicit such protection. As T cells are restricted by proteins called HLAs, which vary across ethnicities, we will define T cell regions for HLAs prominent in Indigenous Australians and define how to generate protective immunity against influenza.
Harnessing Tyrosine Metabolism To Combat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$866,467.00
Summary
Cross-talk between our immune system and the microbiome is central to health and disease. In particular, the gut microbiome has wide-ranging effects throughout the body, in part through the production of metabolites with immunomodulatory activity. We have discovered a novel subset of microbial metabolites which can protect mice against allergic airway inflammation, a model of asthma. We now aim to discovery how these metabolites work with a view towards developing them as therapeutics.