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
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
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.
Genetic Modulation Of The Host Response To Pulmonary TB
Funder
National Health and Medical Research Council
Funding Amount
$540,273.00
Summary
Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host respo ....Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host response contains dormant TB organisms inside activated macrophages. Cells are recruited to wall off infected macrophages and specific T cells continually induce the activate state with minimal tissue damage (immunopathology). Although currently available antibiotics can kill TB organisms, the treatment is prolonged, expensive, difficult to administer in poorly resourced regions and not effective against multi-drug resistant organisms. New therapies to treat both active disease and prevent reactivation in individuals who are latently infected are urgently required. This proposal will address this problem using a novel approach, namely gene manipulation to augment host immunity to TB and limit concurrent immunopathology. We will construct vectors to increase expression of the key immune molecules, the T lymphocyte activating cytokines IL-12 and IL-23, and the macrophage effector molecules LRG-47 and Indoleamine 2,3-Dioxygenase (IDO). These molecules are known to be involved in TB killing. We will determine if increasing their expression increases the killing capacity of TB-infected macrophages and we will examine how these molecules interact to aid clearance of the TB bacilli. This internationally competitive grant will further our detailed understanding of the complex immune response to TB organisms and lead to the development of novel therapies to treat TB infection and prevent reactivation of latent disease.Read moreRead less
There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this proj ....There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this project is to investigate the liver disease caused by HBV in co-infected patients and the development of antiviral resistance due to the long-term treatment with lamivudine. We will develop a data base to monitor virological, biochemical and histological parameters for each of these co-infected patients. We will collate all information on these patients that are attending these various centres. This data base will be essential for monitoring the disease in patients with a poor immune system versus patients with a normal immune system. The HBV virus isolated from these patients will be characterised by sequence analysis. The sequence analysis of these viruses will be compared before and after treatment to determine any resistance markers that have developed. These resistant markers will be copied into an infectious clone using specialised molecular techniques. Clones containing these resistant markers will be analysed in the laboratory to determine the antiviral sensitivity to lamivudine and a number of new drugs against hepatitis B virus. This information will be important in treating patients that are co-infected with HBV and HIV and have already developed resistance to lamivudine.Read moreRead less