Development Of Hepatitis B Surface Antigen As A Generic Vector For The Delivery Of Foreign CTL Epitopes.
Funder
National Health and Medical Research Council
Funding Amount
$439,642.00
Summary
Many kinds of cancer and infections display unique proteins which the body's immune system can recognise as ' foreign', and mount an immune response which, if correctly harnessed, will kill the cancer or infected cells . A way to harness the immune response is to vaccinate with these unique proteins. However, new ways need to be found to deliver the unique proteins to produce the maximal possible anti- cancer or pathogen response, and one that is long lived. In particular one needs to stimulate ....Many kinds of cancer and infections display unique proteins which the body's immune system can recognise as ' foreign', and mount an immune response which, if correctly harnessed, will kill the cancer or infected cells . A way to harness the immune response is to vaccinate with these unique proteins. However, new ways need to be found to deliver the unique proteins to produce the maximal possible anti- cancer or pathogen response, and one that is long lived. In particular one needs to stimulate the cellular arm of the immune response to produce killer cells named CTLs which specifically kill cancer or infected cells. In this project we plan to use an already-licensed human vaccine - the Hepatitis B surface antigen vaccine , or HBsAG, - and genetically modify it to contain important regions of cancer or pathogen proteins termed 'epitopes'. We surmise that immunisation with these modified HBsAg will elicit powerful CTL responses which will killer cancer or infected cells.Read moreRead less
Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Implementing And Enhancing Evidence-based Research And Practice In Hepatology
Funder
National Health and Medical Research Council
Funding Amount
$569,219.00
Summary
The overall aim of this proposal is to tackle unmet challenges in liver disease research. This will be achieved through (a) Population level programs to deliver new treatments for patients with hepatitis C; (b) Developing integrated care models to treat hepatitis B; (c) Developing population-level programs for liver cancer control; and (d) Identification of patients at risk of severe liver disease through understanding the genetic basis of disease progression.
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
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 Role Of Fibroblast Activation Protein In Chronic Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Chronic liver diseases, particularly those caused by Hepatitis B virus and Hepatitis C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. We have identified a key molecule Fibroblast Activation Protein (FAP) that may play a key role and the process of liver fibrosis (scarring). The aims of the project are four fold: (1) ....Chronic liver diseases, particularly those caused by Hepatitis B virus and Hepatitis C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. We have identified a key molecule Fibroblast Activation Protein (FAP) that may play a key role and the process of liver fibrosis (scarring). The aims of the project are four fold: (1) To characterise where and on what cells FAP is produced in the liver and whether FAP levels correlate with the development of fibrosis in human chronic liver diseases caused by either Hepatitis B or Hepatitis C virus infections. (2) To examine a mouse strain in which the FAP molecule is knocked out ie absent. This will tell us whether FAP itself is essential for the development of fibrosis. (3) To isolate the cells within the liver that make FAP and to examine how particular functions of these cells are modified by FAP. (4) To find out what particular molecules FAP acts upon to perform its functions. The achievement of these aims will greatly increase our understanding of this key enzyme and its role in chronic liver injury. This work can potentially lead to the development of specific inhibitors of FAP function designed to relieve liver damage.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.