Developing A Safe Vaccine Against Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$768,530.00
Summary
Group A streptococcus causes 520,000 deaths each year. A safe and effective vaccine is not commercially available. We have identified new protective candidate antigens, and we seek to undertake critical non-human primate studies to provide further proof-of-concept data. This work will underpin commercial decisions by our industry partner (Sanofi Pasteur) leading to human trials and the development of a safe group A streptococcal vaccine for human use.
Clinical And Genomic Aspects Of Staphylococcus Aureus And Other Infectious Diseases In Northern Australia.
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The burden of infectious disease is high in Indigenous populations in northern Australia and patterns of disease differ. My research proposes to deepen our understanding of infectious diseases such as that due to Staphylococcus aureus (golden staph), hepatitis B and influenza by applying cutting-edge technologies (e.g., bacterial genomics) to answer clinically relevant questions. Ultimately I hope to prevent transmission of infections, improve vaccine strategies and find better targets for treat ....The burden of infectious disease is high in Indigenous populations in northern Australia and patterns of disease differ. My research proposes to deepen our understanding of infectious diseases such as that due to Staphylococcus aureus (golden staph), hepatitis B and influenza by applying cutting-edge technologies (e.g., bacterial genomics) to answer clinically relevant questions. Ultimately I hope to prevent transmission of infections, improve vaccine strategies and find better targets for treatment.Read moreRead less
Mathematical Modelling Of Bacterial Carriage In Children
Funder
National Health and Medical Research Council
Funding Amount
$421,746.00
Summary
Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, child ....Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, children attending group child care are at high risk of ear infections. As many bacteria are resistant, antibiotics are now much less effective than when they were first introduced. Furthermore, there is a continuing load of infection for children in Aboriginal communities, in PNG and other developing countries, causing hearing loss, chronic respiratory problems, and heart disease and renal disease in later life. Using data previously collected from other studies in Indigenous communities and children in child care, mathematical models allow us to ask what if?, and answer important public health questions: 1. What environmental and public health measures can reduce the cycle of cross-infection in child-care and high-risk populations? 2. What coverage rates with pneumococcal vaccine will eliminate the vaccine-specific bacteria from child care centres, from the wider community, and from high risk populations? 3. Will infections with bacteria not covered by vaccine then increase? 4. Will the resistant bacteria tend to disappear if antibiotic use is restricted? 5. Under what circumstances will antibiotics help to control infection? The modelling will promote understanding of the social and health costs of bacterial infection in Aboriginal communities and child care and use educational scenarios to promote uptake of the most cost-effective and socially acceptable interventions.Read moreRead less
Investigation Of The Localisation, Transport And Vaccine Potential Of Group A Streptococcal Cell Surface Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$505,523.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represe ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represent candidate vaccine antigens capable of conferring protective immunity. We therefore propose to examine these surface proteins as components of experimental vaccines against GAS.Read moreRead less
Evolution Of Pertussis Epidemics And Effect Of Genotypes On Infection Outcomes And Immunisation
Funder
National Health and Medical Research Council
Funding Amount
$657,781.00
Summary
Pertussis, or whooping cough, is caused by Bordetella pertussis. Despite high vaccine coverage, the incidence of pertussis has increased substantially in recent years in Australia. One of the contributing factors is changes in the pertussis strains. This project will determine the genetic composition and virulence characteristics of epidemic strains in Australia and investigate the effect of these strains on disease severity and vulnerability of vaccinated individuals to infection.
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
Nasal Epithelium As A Portal Of Entry For Burkholderia Pseudomallei, With Special Reference To Neurological Melioidosis
Funder
National Health and Medical Research Council
Funding Amount
$536,419.00
Summary
Melioidosis is a potentially fatal disease of manly tropical Australia and SE Asia and an emerging disease worldwide. It disproportionately affects indigenous Australians. It is caused by a bacterium found in soil and water and infection may be by inhalation in the rainy season. One manifestation of melioidosis is neurological symptoms. This project seeks to establish sites and pathways of infection resulting from inhalation, including the pathway from nasal mucosa to brain.
Functional characterisation of poly-histidine triad proteins. This project aims to understand the role and function of a novel family of surface proteins produced by Streptococci. These so-called polyhistidine triad proteins are known to contribute to capacity to cause disease in animals and humans, but we need to know how they work, as they may be excellent targets for novel drugs or vaccines.
Novel perspectives on the function of AB5 toxin B subunits in pathogenic bacterial. AB5 toxins are produced by bacteria that cause important diseases in humans and livestock. This project tests the hypothesis that the components of the toxins responsible for binding to host cells and tissues also directly contribute to cellular damage, thereby providing a better understanding of how AB5 toxin-producing bacteria cause disease.
How bacteria cause disease in the urinary tract. This project will investigate the virulence properties of uropathogenic Escherichia coli, the major causative agent of urinary tract infections (UTI) in humans. The results will help to understand how these bacterial pathogens cause disease and will impact strategies aimed at the prevention and treatment of chronic and recurrent UTI.