A Universal Prophylactic Vaccine For Hepatitis C Virus
Funder
National Health and Medical Research Council
Funding Amount
$643,337.00
Summary
Hepatitis C Virus (HCV) infects 200 million people world wide. An effective vaccine to prevent HCV is urgently needed but must afford protection against the 7 diverse genotypes. In this project grant we aim to further define the quality of the immune response that is generated by a novel HCV vaccine candidate that generates pan-genotypic immunity, its unique structural features, and methods of manufacturing so that it can be tested in a future phase I human clinical trial.
A Novel Vaccine Platform For Trimeric Envelope Proteins: HIV-1 Envelope
Funder
National Health and Medical Research Council
Funding Amount
$139,250.00
Summary
Vaccines are urgently needed for the prevention of HIV/AIDS. The design of this vaccine candidate is based on the display of HIV-1 envelope spikes using a related primate retrovirus envelope with a more stable assembly to anchor the the spikes in a particle.
Kunjin Virus Replicon-based Vaccine Vectors: New Developments And Applications
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The project is aimed towards further development of a unique gene expression and delivery system based on self-replicating RNA (replicon) of the nonvirulent Australian flavivirus Kunjin (KUN). A number of improvements in the design of KUN replicon vectors aimed to increase their efficiency and to optimize them for production of heterologous gene products with desired terminal sequences are proposed. Also proposed are improvements in the current KUN replicon packaging system and development of ne ....The project is aimed towards further development of a unique gene expression and delivery system based on self-replicating RNA (replicon) of the nonvirulent Australian flavivirus Kunjin (KUN). A number of improvements in the design of KUN replicon vectors aimed to increase their efficiency and to optimize them for production of heterologous gene products with desired terminal sequences are proposed. Also proposed are improvements in the current KUN replicon packaging system and development of new packaging systems for production of large amounts of virus-like particles (VLPs) containing KUN replicon RNA enclosed in KUN coat proteins for use as potential vaccines. The vaccine potentials of the curent and newly developed KUN vectors and VLPs will be evaluated in mice using respiratory syncytial virus as a model. An entirely new direction proposed in this application is generation of chimeric fowlpox virus-KUN replicon vectors which will combine the advantages of both systems and may result in the generation of an ultimate vaccine vector.Read moreRead less
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
Long-lived CD8 T Cell Responses Induced By A Recombinant Cytomegalovirus Vector
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
The priming of the immune system to protect against infection and disease is an important means to alleviate these conditions. Current vaccination technologies often rely on multiple inoculations (prime-boosting). In addition, specific priming of the immune system against pathogens that target mucosal sites has been difficult and often lacks efficacy resulting in temporary or variable protection. Using a well developed mouse model for a common human virus, we have explored the potential of this ....The priming of the immune system to protect against infection and disease is an important means to alleviate these conditions. Current vaccination technologies often rely on multiple inoculations (prime-boosting). In addition, specific priming of the immune system against pathogens that target mucosal sites has been difficult and often lacks efficacy resulting in temporary or variable protection. Using a well developed mouse model for a common human virus, we have explored the potential of this agent as a vaccine agent, making use of its long term persistence in the infected host to provide continued antigenic stimulation of the immune system. We have found that very strong and long lasting responses can be elicited after a single inoculation of avirulent virus. In this study, this effect will be further explored and developed.Read moreRead less
Immune Therapies For Chronic Hepatitis B Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$359,085.00
Summary
Hepatitis B virus (HBV) causes acute and chronic infection leading to severe liver damage in many patients and increased risk of primary liver cancer. Worldwide ~350 million people have chronic HBV infection and, while a HBV vaccine is available that protects against new infections, current antiviral drug treatments for existing infection are largely ineffective. Thus, the aim of our project is to develop new treatments for chronic HBV infection using vaccination approaches. These therapies will ....Hepatitis B virus (HBV) causes acute and chronic infection leading to severe liver damage in many patients and increased risk of primary liver cancer. Worldwide ~350 million people have chronic HBV infection and, while a HBV vaccine is available that protects against new infections, current antiviral drug treatments for existing infection are largely ineffective. Thus, the aim of our project is to develop new treatments for chronic HBV infection using vaccination approaches. These therapies will be tested in ducks infected with the duck hepatitis B virus (DHBV), a model for human HBV infection. In brief, DHBV-infected ducks will be treated with a new antiviral drug, Entecavir (ETV) developed by Bristol-Myers Squibb, which blocks virus replication. To accelerate clearance of infected cells before drug-resistant viruses can emerge, the ducks will also be treated in combination with different novel therapeutic vaccines designed to induce strong humoral and cell mediated immune responses. Based on outcomes in initial experiments, we will adjust the vaccination protocol in ETV-treated ducks to maximize reductions in the levels of DHBV in liver and bloodstream, rates of death and clearance of DHBV-infected hepatocytes. Our ultimate goal is to define a protocol for combination antiviral and vaccination treatments that allows elimination of HBV infection, or that achieves a level of control of infection that eliminates ongoing disease by reducing virus loads to virtually undetectable levels.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