CLINICAL RESEARCH TO UNDERSTAND ACQUIRED IMMUNITY TO DENGUE VIRUSES
Funder
National Health and Medical Research Council
Funding Amount
$841,953.00
Summary
Dengue, the commonest arboviral disease of humans, is caused by any of the four serotypes of dengue virus (DENV-1-4). This clinical research project will explore how acquired immunity to dengue viruses is expressed. The results will help dengue vaccine developers make better vaccines for use in Australian travellers and in dengue endemic countries in SE Asia.
Profiling The Specificity Of The Neutralizing Antibody Response In People Who Have Long Term Protection From Developing Chronic HCV
Funder
National Health and Medical Research Council
Funding Amount
$372,972.00
Summary
Hepatitis C causes chronic liver disease in over 150 million people world-wide. In this study we will determine the qualities of the immune response that protect individuals from HCV infection and reinfection. The outcomes of this study will provide a pathway for the development of vaccines that elicit protective immune signatures.
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.
Prophylactic Vaccine Development For The Elimination Of Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$936,752.00
Summary
A vaccine that prevents Hepatitis C is urgently needed to prevent infection and assist with global HCV elimination targets. This project grant will advance world-leading HCV vaccine candidates that generate both humoral and cellular immunity for clinical development.
Novel HIV-1 Glycoprotein Vaccines With Enhanced Presentation Of Broad Neutralization Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$743,682.00
Summary
A prophylactic vaccine represents the best strategy for blocking HIV-1 transmission but one is not yet available. Current antiviral vaccines rely on neutralizing antibodies (NAbs) that block infection, however, current HIV-1 vaccine formulations do not induce broadly reactive NAbs (bNAbs). We have discovered a novel HIV-1 glycoprotein vaccination candidate with enhanced presentation of bNAb epitopes. We propose to determine if this vaccine induces effective bNAbs in experimental animals.
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
Roles Of The Hepatitis C Virus Glycoprotein E2 Variable Regions In Virus Entry, Immunogenicity And Immune Evasion.
Funder
National Health and Medical Research Council
Funding Amount
$682,820.00
Summary
Hepatitis C Virus infects 200 million people world-wide with over 200,000 Australians infected with the disease. This project will examine how the surface proteins of HCV change their shape to evade antibody responses and how this effects the outcome of infection. We will further characterize a vaccine that elicits protective immunity to HCV to identify the optimal formulation for clinical trials.
Detailed Investigation Of The Humoral Immune Response To HCV To Identify Diagnostic And Prognostic Serological Markers
Funder
National Health and Medical Research Council
Funding Amount
$387,466.00
Summary
The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the d ....The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the different stages of infection. The expected outcomes of this study include the identification of a marker of recent Hepatitis C infection. This will permit accurate epidemiological monitoring of Hepatitis C, better design of programs to control the spread, trace outbreaks and manage treatment programs. The identification of a marker capable of predicting the clinical outcome of infection would be invaluable to clinicians, because following acute infection with Hepatitis C, 20 to 30% of individuals will resolve their infection without the need for therapeutic intervention. The information obtained in this study will also lead to a better interpretation of diagnostic laboratory findings, improving our ability to provide clear and accurate reports to blood donors and consequently enhance the Australian blood supply in terms of safety and donor retention.Read moreRead less
Characterization Of Neutralizing Antibody Responses In HCV Infected Individuals.
Funder
National Health and Medical Research Council
Funding Amount
$478,076.00
Summary
Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attri ....Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attributed to the development of a strong cellular immune response and antibody is belived to play a monir role in achieving viral clearance. However, measurememnt of antibody responses in HCV infected pateints is routinely performed using conventional diagnostic tests that do not measure antibody that can help neutralize and clear virus. We have developed an assay that accurately measures the level of NAb in patient sera. We have found that chronically infected patients have broadly reactive neutralizing antibodies but that patients who clear virus, naturally or through treatment do not have broadly reactive neutralizing antibodies. Possibly explaining this phenomenon is that early during infection, antibody is frequently specific only to the infecting virus therefore to detect neutralizing antibodies, homologous viral sequences must be examined. In addition, we have found evidence that HCV can evade neutralzing antibodies through masking of sites to which antibodies bind. We propose to explore whether acutely infected patients develop NAb to autologous viral sequences, and how do these viral sequences and the antibody titre change throughout the course of infection and treatment. We also plan to determine the mechanism of neutralization resistance through the use of mutagenesis of resistant HCV glycoproteins. These studies are aimed at gaining a thorough understanding of the true role of antibody in HCV infection and its influence on viral evolution.Read moreRead less