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
Identification Of Interferon Stimulated Genes That Limit HCV Replication And Predict Therapeutic Outcome
Funder
National Health and Medical Research Council
Funding Amount
$389,224.00
Summary
The only treatment for hepatitis C is Interferon-ribavirin combination therapy. Interferon works by stimulating the liver cells to produce antiviral proteins that can control hepatitis C virus replication, however we do not know which proteins are responsible. The aim of this proposal is to identify those proteins that can limit HCV replication using both a laboratory based and clinical approach and to identify markers that will predict treatment outcome.
Identifying The Social, Personal And Health Needs Of Men Living With Hepatitis C.
Funder
National Health and Medical Research Council
Funding Amount
$215,906.00
Summary
This study will identify the health and social support needs of men who are infected with hepatitis C and will complement a similar study currently being conducted with women. At present, there is little information about the ways that hepatitis C impacts on the lives of men and research on the impact of related diseases (HIV-AIDS) strongly suggests that hepatitis C is likely to affect men in different ways to women, both economically, personally and physically. This is further complicated by th ....This study will identify the health and social support needs of men who are infected with hepatitis C and will complement a similar study currently being conducted with women. At present, there is little information about the ways that hepatitis C impacts on the lives of men and research on the impact of related diseases (HIV-AIDS) strongly suggests that hepatitis C is likely to affect men in different ways to women, both economically, personally and physically. This is further complicated by the fact that the majority of infected men have a history of injecting drug use, which coupled with the stigma often attached to chronic diseases such as hepatitis C, negatively impacts on men's lives. Of specific concerns are issues around employment, access to appropriate health care and social support. Six hundred men from Melbourne and regional Victoria will be surveyed. We will ask them questions about the social and personal impact of HCV on relationships with partners, the availability and accessibillity of appropriate treatment, care and support services and other ways that living with hepatitis C has affected their lives. The findings of this study will be used to help policy makers and service providers make decisions about education, support and care services so that they best suit the needs of men who have hepatitis C.Read moreRead less
Hepatitis C Vaccine Preparedness Study: Investing In Infectious Disease Prevention
Funder
National Health and Medical Research Council
Funding Amount
$820,767.00
Summary
Injecting drug users (IDU) are a key target group for new vaccines designed to prevent hepatitis C virus (HCV) infection. This study will establish the feasibility of conducting HCV vaccine trials in IDUs by answering key scientific questions, generating data to inform trial design and evaluation, establishing a partnership between leading international researchers and the peak Australian body for people who inject drugs, and providing the foundation for a global HCV prevention trial network.
Mechanisms Underlying Growth, Lineage Commitment And Differentiation Of Liver Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Liver disease is a serious health problem. Viral hepatitis, obesity and alcohol can result in end-stage liver disease. Organ transplant is the only treatment available. A widening gap between organ donations and recipients mandates alternative treatments are developed. Cell transplantation and artificial liver devices are alternatives which can use liver progenitor cells. We will investigate how factors grow and convert them into liver cells for treating liver disease patients.
Adaptation Of Hepatitis C To Host HLA-Restricted Immune Responses In Australian Populations
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Over 200,000 Australians are infected with the Hepatitis C Virus (HCV) and about 11,000 new infections are diagnosed each year. Around 25% of people infected with HCV will clear the virus while for individuals with chronic infection 10 to 20% will develop cirrhosis of the liver within the next 20-40 years. Differences in host genetic factors and viral variants will, in large part, explain the observed heterogeneity in the clinical outcome and course of HCV infection. The basic theory underpinnin ....Over 200,000 Australians are infected with the Hepatitis C Virus (HCV) and about 11,000 new infections are diagnosed each year. Around 25% of people infected with HCV will clear the virus while for individuals with chronic infection 10 to 20% will develop cirrhosis of the liver within the next 20-40 years. Differences in host genetic factors and viral variants will, in large part, explain the observed heterogeneity in the clinical outcome and course of HCV infection. The basic theory underpinning this research is that the evolution of viruses such as HCV and HIV are influenced by the HLA type of the individual (hots), in combination with the ability of the virus to mutate (rid itself of deleterious mutations) to avoid the host's immune challenge (analogous to drug resistance) even at the lesser cost of impairing viral fitness or replication. We have shown that this is dependent on the immune environment that the virus encounters in relation to which HLA alleles are present in the host, therefore the escape is context specific. After transmission to a new host who lacks the same HLA type, the virus eliminates the previously advantageous mutations which could potentially impair viral fitness. The current study will carry out HCV sequencing and HLA typing on approximately 500 people with HCV from multiple Centres in Australia in order to characterise the interaction between the viral and host genetic factors. A customised software programme, Epipop, has been designed to perform sophisticated statistical analyses on the generated data, and has been successfully applied to HIV vaccine design. The results of this study could help explain why some infected individuals can spontaneously clear their infection while others go on to severe liver disease and allow clinicians to anticipate the course of infection in individuals and plan their management accordingly. Furthermore, the results may facilitate the search for optimal therapeutic and vaccination strategies.Read moreRead less
Role Of The Hepatitis C Virus Glycoprotein E2 Variable Regions In Viral Entry And Antibody Mediated Neutralization.
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
The first stage of Hepatitis C Virus replication involves attaching to liver cells. This study is aimed at understanding how the virus attaches to liver cells and how antibodies raised during infection, block this interaction. In addition, this study aims to examine how the virus modulates its structure to evade the immne system, allowing the virus to establish chronic infections. The results of this study will guide future vaccine design for HCV.