The In Vitro Culture Of Hepatitis C Virus And Approaches To The Control Of Replication
Funder
National Health and Medical Research Council
Funding Amount
$452,310.00
Summary
HCV is a major cause of liver disease and around 200 million people are currently infected worldwide, including 200,000 Australians. HCV differs to other flaviviruses. Most notably, around 80% of individuals develop a persistent infection, accounting for the large number of carriers. This infection is probably life-long and 40-50% of carriers will develop serious liver disease, including liver cancer. HCV is currently the leading single indicator for liver transplantation in the western world. T ....HCV is a major cause of liver disease and around 200 million people are currently infected worldwide, including 200,000 Australians. HCV differs to other flaviviruses. Most notably, around 80% of individuals develop a persistent infection, accounting for the large number of carriers. This infection is probably life-long and 40-50% of carriers will develop serious liver disease, including liver cancer. HCV is currently the leading single indicator for liver transplantation in the western world. These carriers can also transmit the virus to uninfected individuals. Screening in the blood banks has reduced transmission after blood transfusion to virtually zero. However, although individuals who share contaminated needles represent a major high risk population, around 30% of carriers have no acknowledged transmission risk factors, and transmission to patients in hospitals has been recognised. As a result, it is clear that members of the general population may still become infected. It has been estimated that there are 10,000 new cases each year in Australia. The best available treatment is a combination of interferon-alpha and ribavirin, but this is only successful in 40-50% of carriers. Moreover, many patients fail to tolerate these drugs and the cost restricts treatment to a small proportion of carriers. As a result,only approx 6,500 carriers have been treated in Australia. A huge backlog in the liver clinics and the resistant nature of the virus in 50% of patients in Australia mean that these patients will not be treated unless new therapies are developed. The most effective means to prevent virus infections is by vaccination. Thus the development of novel antivirals and a vaccine for HCV are priorities. Since the cost of a single liver transplant is $100,000 the development of such agents is likely to be cost effective. However, it is necessary to develop suitable cell culture systems to test putative antiviral agents.Read moreRead less
Synthesis And Purification Of Flavivirus-specific Antiviral Factor Mrasal
Funder
National Health and Medical Research Council
Funding Amount
$140,000.00
Summary
In this proposal we suggest to develop an anti-flaviviral compound based on naturally occurring host factors associated with inborn flavivirus resistance observed in mice. We propose to synthesise and purify a mouse protein factor encoded by a gene (Mrasal), which we have previously mapped by mouse genetics and positional cloning to a narrow 300 kb chromosomal region on mouse chromosome 5 carrying flavivirus resistance locus (Flv). When this mouse gene was isolated, sub cloned into a mammalian e ....In this proposal we suggest to develop an anti-flaviviral compound based on naturally occurring host factors associated with inborn flavivirus resistance observed in mice. We propose to synthesise and purify a mouse protein factor encoded by a gene (Mrasal), which we have previously mapped by mouse genetics and positional cloning to a narrow 300 kb chromosomal region on mouse chromosome 5 carrying flavivirus resistance locus (Flv). When this mouse gene was isolated, sub cloned into a mammalian expression vector pcDNA3tag and transiently transfected and expressed in cos-7 and Vero cells, its product conferred antiviral effect to a flavivirus Murray Valley encephalitis (MVE), but not to a non-flavivirus encephalomyocarditis virus (EMCV). Mrasal protein operates as an antiviral host factor and confers a flavivirus specific resistance at the cellular level. It could be directly used for the treatment-cure of acute flavivirus infections in vivo. Our aims are to produce and purify the Mrasal protein for the in vivo delivery as a therapeutic compound into susceptible mice during the acute phase of flavivirus infection: 1. To synthesise and purify Mrasal protein using baculovirus system. 2. To encapsulate the protein into liposomes ready to be used in mice. 3. To perform initial testing in a limited number of susceptible mice.Read moreRead less
A New Scrambled Antigen Vaccine (SAVINE) Approach: Proof-of-concept In Non-human Primates For HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$120,700.00
Summary
The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of H ....The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of HIV-1 to provide universal coverage of the major HIV-1 strains for a global population. The synthetic systematically designed HIV-1 vaccine will be delivered using our newly developed prime-boost immunisation regime that induces particularly high levels of cell-mediated immunity.Read moreRead less
Hypoallergenic Proteins As Novel Immunotherapeutic Candidates For Food Allergy
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
The rate of food allergy has tripled over the past decade and is a leading cause of food related anaphylaxis in Australia. Allergen immunotherapy can help patients develop tolerance to the allergenic food. This research will investigate the potential of hypoallergenic derivatives of two major food allergens as novel desensitisation therapeutics, addressing an issue of significant importance to human health, paving the way for research on advanced therapeutics for paediatric food allergy.
Characterisation Of A Novel Direct Electrochemical Chip As A Biosensor And Tool For Studying Redox-sensitive Proteins
Funder
National Health and Medical Research Council
Funding Amount
$144,500.00
Summary
Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advanc ....Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advance in biosensing capabilities using a recombinant protein (thioredoxin) and demonstrated the improvement that is possible by (i) immobilising the protein in a highly oriented way and (ii) using a sensitive electrical signal to monitor the response. Here we will undertake more comprehensive testing by extending the number of proteins to include the 4 major classes of redox-sensitive biomolecules (proteins) in the body. This will enable us to establish the broad application of our methods and substantially improve our ability to commercialize our discoveries.Read moreRead less