Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients ....Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients with chronic infection are expected to die prematurely due to chronic liver disease or primary liver cancer. Interestingly, exposure to HBV can lead to either acute resolving or chronic HBV infection. Like chronic infections, acute infections involve spread of virus to virtually every hepatocyte, followed by rapid clearance of the virus mediated by the host immune response. Our immediate aim is to study the resolution of acute HBV infections to determine how the stable intracellular viral genome, covalently closed circular DNA (cccDNA), is cleared from the nucleus of infected hepatocytes. Our broad long-term aim is to develop new and effective treatments for chronic HBV infection based on a better understanding of how acute HBV infections are resolved by the host. Based on our previous work we believe that clearance of cccDNA requires hepatocyte death, together with compensatory proliferation of other infected hepatocytes. We will perform detailed studies in duck hepatitis B virus (DHBV) infected ducks to determine if hepatocyte death and compensatory proliferation are essential to clear the infection, or if mechanisms exist for clearance that do not involve cell destruction.Read moreRead less
Self Adjuvanting CTL-Based Influenza Vaccines For Human Use
Funder
National Health and Medical Research Council
Funding Amount
$214,842.00
Summary
This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recog ....This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recognised by specific receptors on the surface of dendritic cells and also causes their maturation, a step which is essential for recognition by the immune system of potential pathogens. The technology to design and assemble these new vaccines is already.Read moreRead less
A Randomised Open-label Study Comparing The Safety And Efficacy Of Two Alternative Treatment Options In The Management Of HIV-1 Infected Participants Who Have Virologically Failed A Standard First-line Combination ART Regimen
Funder
National Health and Medical Research Council
Funding Amount
$457,676.00
Summary
For the past decade there has been an unprecedented international effort to provide access to care for all HIV-infected people as a basic human right. Most of these people are treated with a simple combination of drugs that are well proven to control HIV. However, what to do when this first drug combination stops working is unknown. This study aims to fill that knowledge gap so that patients failing the first drug combination can be offered a second combination with a maximal chance of success.
Application Of Mathematical Modelling And Development Of Decision Support Tools For Mosquito-borne Disease
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Mosquito-borne disease affects millions of people in Australia and overseas. Reducing the prevalence of these diseases requires an understanding of their transmission, drug resistance and role of external factors such as climate. This project will use newly developed mathematical and statistical tools to investigate transmission of malaria, and improve the reporting of Ross River and Barmah Forest viruses and dengue. Project outcomes will assist the development of evidence based policy.
An In Depth Analysis Of Clinical And Virological Outcomes Of 2 Strategies For The Antiretroviral Salvage Of First-line Regimen Virological Failure For HIV-1 Infection Tested In An Australian-led Randomised, International, Multi-centre Clinical Trial
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The recently completed Australian-led SECOND-LINE trial is the first high quality study to provide reliable evidence for policy recommendations for the composition of anti-HIV drug cocktails after standard initial treatment has failed. This award will support the researcher in further refining our understanding of how to manage second-line therapy including proposals to test the use of low-cost technologies for application in resource-limited settings where the majority of people with HIV live.