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Towards A Functional Cure For HBV: Exploiting Lessons From HBV-HIV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$913,551.00
Summary
Hepatitis B virus (HBV) infection can be treated, but therapy is usually lifelong and has side effects, so a cure for HBV is very important. We work closely with colleagues in Asia where both HBV and HIV are common so this provides a unique opportunity to study HBV. We will investigate how an effective immune response against the 2 main HBV proteins is developed. If we can understand how the immune response works against HBV, this could be used to develop new therapies to develop a cure for HBV
I am an infectious diseases physician and basic scientist interested in the immunopathogenesis of HIV and hepatitis B virus. My work focuses on HIV viral reservoirs and immune reconstitution and the adaptive immune response to hepatitis B virus.
Suppression Of Immune Toll-like Receptor (TLR) Signaling By Hepatitis B E Antigen (HBeAg)
Funder
National Health and Medical Research Council
Funding Amount
$542,320.00
Summary
Hepatitis B virus (HBV) infection is a major world-wide health problem, which the current treatment strategies are not ideal. Therefore understanding how HBV inteacts with the immune system is of critical importance to developing intervention strategies to promote better health outcomes. This grant will develop our novel findings that a protein produced by HBV 'blinds' the host immune system by producing a protein that blocks the innate immune response to allow HBV to replicate unchallenged.
Hepatitis B Virus Immunity In Indigenous And At Risk Children Who Received Hepatitis B Vaccination In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$213,762.00
Summary
Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of ....Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of origin, (including Aboriginal- Torres Strait Islanders) and infants whose mother was a HBV carrier. These children, among the first to be vaccinated, are now adolescents. There have been no long-term follow-up studies in Australia, and limited studies elsewhere, to assess the extent of breakthrough infection and persistence of immunity to Hepatitis B after vaccine at birth. As onset of sexual activity is associated with an increased exposure to hepatitis B infection, booster doses may be needed, especially in high-risk individuals. This study includes 2 high risk groups - young indigenous adults in the Northern Territory and young adults born to HBV carrier mothers in central Sydney. It will measure the number of children who have been infected with HBV or are chronic carriers, compared to pre immunisation data, and also the persisting level of immunity in children who were vaccinated against HBV as an infant. Children whose blood test indicates that they have low immunity will be given a booster dose of HBV vaccine and their immune response measured. A rise in hepatitis B antibody following booster vaccination indicates that you have immunological memory and is currently considered to show protection from natural hepatitis B infection. If clinically significant HBV infections are found to be rare and immunologic memory can be demonstrated, this would provide good evidence to support the argument that booster vaccine doses are not required in the Australian context.Read moreRead less
Characterisation Of Immune Responses To Sarcoptes Scabiei Cysteine Proteases, Group 1 Allergen Homologues, In Scabies
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly ....Scabies, a parasitic skin infestation by the 'itch' mite Sarcoptes scabiei, causes significant health problems for children and adults in many remote Aboriginal communities in Australia. Scabies is often the underlying cause of streptococcal skin infections which can cause serious complications such as kidney and heart disease. Although diagnosed scabies cases can be successfully treated, individuals have often already transmitted the disease to others prior to receiving therapy. A particularly dreadful form of scabies, known as crusted scabies, can develop in a minority of people, in which mites multiply in their millions and the affected person develops severe crusting of the skin. This has resulted in death within 5 years for up to 50% of people with this form of scabies. Scabies mites are scientifically very similar to house dust mites, and they produce cross reactive proteins. Molecular studies in our laboratory have enabled the identification and cloning of a number of scabies molecules with considerable similarity to known house dust mite proteins that cause allergic disease. In this study we propose to focus on a group of scabies proteins with significant identity to the extensively studied Group 1 house dust mite allergens, reported to cause an immune response in 90% of mite allergic people. We propose to use these scabies mite molecules to characterise the immune response in ordinary scabies and compare it to the more severe and debilitating crusted form of the disease. Characterisation of the immune response in scabies will ultimately aid in the development of new treatment for crusted scabies based on immunotherapy. Studies will also investigate for any cross reactivity with the house dust mite group 1 molecules and enable the design of specific immunodiagnositics to distinguish house dust mite allergy from scabies infestation and thus facilitate early diagnosis of scabies carriers and better control of the infestation in endemic communities.Read moreRead less
I am infectious disease physician undertaking research on natural history and therapeutic strategies in viral hepatitis, including acute hepatitis C, chronic hepatitis C and chronic hepatitis B. The hepatitis C therapeutic research has a particular focus
A vaccine against the bacteria Group A streptococcus (‘strep’) could prevent common minor infections like sore throat and school sores as well as deadly ones like necrotising fasciitis (‘flesh eating disease’). It would also reduce long-term heart (rheumatic heart disease) and kidney problems. We are going to try and deliberately give a sore throat to adult volunteers under very close medical supervision so that we can learn more about immunity to strep and to help make and test new vaccines.
The Future Of HIV Care - Long Term Remission And Eliminating Co-morbidities
Funder
National Health and Medical Research Council
Funding Amount
$577,189.00
Summary
Despite the great successes in antiretroviral therapy (ART) in reducing HIV-associated mortality, treatment is life long and there is no cure. The major barrier to a cure for HIV is the persistence of long lived latently infected cells on ART. Over the next five years I will discover, develop, optimise and evaluate novel interventions to eliminate latently infected cells, long lived infected cells in the liver and enhance HIV-specific immunity through immunotherapy.
Long Term Persistence Of HIV In The Liver And The Clinical Impact On HIV-HBV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$1,393,245.00
Summary
This grant will address a major question in HIV cure research - the role of the liver as an HIV reservoir and the impact of HIV persistence in HIV-infected patients on suppressive antiretroviral therapy (ART) on liver disease, in the setting of HIV-HBV co-infection. We will trial a novel intervention to reduce HIV infection of the liver that could potentially reduce chronic liver disease in this setting.