A New Insight Into Hepatitis B Infection:the HBV Fusion Peptide
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Three hundred and fifty million people worldwide and 250,000 in Australia are chronically infected with hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current therapies are inadequate. New antiviral treatments requiring the identification of new antiviral targets are needed to combat the disease but a major obstacle to the study of HBV is the lack of a cell culture system. As a result n ....Three hundred and fifty million people worldwide and 250,000 in Australia are chronically infected with hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current therapies are inadequate. New antiviral treatments requiring the identification of new antiviral targets are needed to combat the disease but a major obstacle to the study of HBV is the lack of a cell culture system. As a result nothing is known about how HBV enter and fuses with the host liver cell but we have made significant progress with the identification of the entry and fusion events of the related duck hepatitis B virus, using the duck infection model. This knowledge is now ready for application to the medically important HBV by use of primary human liver cells and the techniques developed in the duck hepatitis B virus model.Read moreRead less
Worldwide >360 million people have chronic hepatitis B virus (HBV) infection that imparts a 25% lifetime risk of death due to serious liver disease. Current therapies for chronic HBV reduce levels of virus replication but fail to target the stable, nuclear episome, covalently closed circular DNA (cccDNA). The current study will determine what is required to eliminate cccDNA and how current therapies for chronic HBV infection should be modified to achieve this aim.
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.
Hepatitis B Virus Drug Resistance: Impact On The Immunisation Program
Funder
National Health and Medical Research Council
Funding Amount
$113,322.00
Summary
ñAntiviral drug-associated vaccine escape mutantsî have the potential to jeopardize the hepatitis B immunization program. Which particular viral mutations or combination of mutations that can directly affect the clinical outcome of infection, especially in the context of vaccine induced immunity, are not known. In this study we will identify the clinical sequelae and public health consequences arising from the selection of these mutants.
Clearing Chronic Infectious Diseases – Enhancing Host Immune Effector Function
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Chronic infections produced by pathogens such as HIV, overwhelm our immune system leading to an exhausted state where cells responsible for the clearance of invading microorganisms are unable to respond effectively. We have recently identified a highly promising therapeutic target that enhances immune effector function. We seek to understand the underlying mechanism, and to explore the therapeutic potential of this approach for the treatment of a broad range of pathogens, including those respons ....Chronic infections produced by pathogens such as HIV, overwhelm our immune system leading to an exhausted state where cells responsible for the clearance of invading microorganisms are unable to respond effectively. We have recently identified a highly promising therapeutic target that enhances immune effector function. We seek to understand the underlying mechanism, and to explore the therapeutic potential of this approach for the treatment of a broad range of pathogens, including those responsible for chronic disease.Read moreRead less
Novel Generic Vaccine Approaches Applied For The Prevention Of Hepatitis C And Influenza Virus Infections.
Funder
National Health and Medical Research Council
Funding Amount
$392,328.00
Summary
For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are maj ....For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are major human pathogens. HCV has infected 200 million people worldwide, and there is no effective vaccine available. Influenza continues to affect thousands of people each year causing epidemics with severe morbidity and considerable mortality. Current influenza vaccines are mostly inactivated formulations and they exhibit poor immunogenicity in immunological naive persons such as children and in the elderly. The influenza vaccines are not optimal for stimulation of cell-mediated immunity. We propose to use particulate antigens as a delivery platform for influenza and HCV-specific epitopes with the focus to develop approaches to target various HCV and influenza strains, including H5N1 bird influenza. We have successfully produced modified VLPs containing HCV-specific sequences, which are able to induce anti-HCV antibodies with neutralising capacity. We hypothesise that the design of VLPs with an appropriate set of HCV-specific antigens will enhance the neutralising capacity of anti-HCV sera and this may overcome strain specificity. This application will exploit a prototype delivery system to induce antibody and also cellular responses against a variety of HCV- and influenza specific target sequences (epitopes). The outcome of this study will be a prototype multivalent vaccine to a range of HCV- and influenza-specific epitopes. As a delivery system this will be ideal for vaccination against agents that are highly variable.Read moreRead less
Novel Early Detection Strategy For Liver Cancer Using Hepatitis B Splice Variants To Expediate Diagnosis And Improve Treatment Outcome
Funder
National Health and Medical Research Council
Funding Amount
$943,566.00
Summary
Hepatitis B virus (HBV) causes liver cancer, which is one of the only cancers that is increasing in prevalence. We have shown that smaller versions of HBV, termed splice variants, are even more strongly associated with liver cancer- people with higher levels of the splice variants were over 3 times more likely to have liver cancer. We will find out why, by thoroughly studying how the splice variants alter the virus and the host cell to promote liver cancer.
Chronic Active Viral Persistence Versus Host Immune Mediated Pathology: An Analysis And Manipulation Of The Balance.
Funder
National Health and Medical Research Council
Funding Amount
$418,658.00
Summary
Our robust ability to mount an immune response and clear infections is tempered by the possibility of promoting autoimmunity. Several host genes regulate immunity. Viruses like HIV have exploited these to abrogate antiviral immunity. This project attempts to define host factors that promote chronic infection. This will be extremely valuable in understanding the vulnerabilities of our immune system and provide an insight into how we can treat chronic infections.
Improved Health Outcomes For People Living With HIV
Funder
National Health and Medical Research Council
Funding Amount
$560,284.00
Summary
Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected wi ....Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected with hepatitis B virus (HBV)Read moreRead less
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.