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
The Role Of Varicella Zoster Virus In Modulating Cutaneous Infection
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
Varicella zoster virus (VZV) causes two skin diseases: chickenpox and shingles. VZV can causes significant morbidity in children and adults and life-threatening disease in immunocompromised people. This project aims to improve our understanding of how VZV affects the function of specialised skin cells to provide information for the development of a better vaccine to lessen the impact of VZV disease on the community.
Understanding And Modulating Hyperinflammation Caused By Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
In humans, highly pathogenic influenza A virus (IAV) infections can be fatal, as the disease is untreatable with available vaccine or anti-viral drugs. My fellowship aims to advance our knowledge of the mechanisms by which the immune system induces and regulates inflammation during IAV infection, which can be both helpful and detrimental in fighting the infection. This is critical for identifying and developing new therapies for severe IAV infections in the future.
Comparative Expression Studies To Identify Cellular Factors Promoting Hendra Virus Replication For A Comprehensive Understanding Of Hendra Virus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$374,619.00
Summary
Hendra virus (HeV) is an emerging pathogen indigenous to fruit bats. HeV is associated with limited outbreaks with high mortality in domesticated animals and humans. To advance the understanding of HeV-related pathogenesis, we will perform comparative studies in bat and human cell lines to recognise differences in virus-host cell interactions leading to a comprehensive understanding of the HeV life cycle and pathogenesis.
HIV is a rapidly evolving virus, and within an infected individual it continually acquires new mutations and joins together mutations by recombination. We have developed a novel system for studying recombination, and find that different individuals have different recombination rates, which may contribute to why some individuals survive longer. This project aims to identify the mechanisms responsible for differing recombination rates and how we can alter these to improve patient outcome.
Defining Key Mechanisms That Underpin Neuropathogenesis Of Varicella Zoster Virus During Herpes Zoster
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Varicella zoster virus (VZV) is a herpesvirus which causes chicken pox and shingles. Shingles affects many elderly people and a major complication is prolonged severe neuropathic pain, often needing follow-up medical care for months to years. Despite its impact on the community, little is known about how this virus functions and causes disease. We aim to improve our understanding of how VZV interacts with nerve cells to provide essential new information for the development of effective treatment ....Varicella zoster virus (VZV) is a herpesvirus which causes chicken pox and shingles. Shingles affects many elderly people and a major complication is prolonged severe neuropathic pain, often needing follow-up medical care for months to years. Despite its impact on the community, little is known about how this virus functions and causes disease. We aim to improve our understanding of how VZV interacts with nerve cells to provide essential new information for the development of effective treatments for shingles and associated neuropathic pain.Read moreRead less
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.
The Role Of Glycans In Arboviral Disease; From Immunomodulation To Glycotherapeutic Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Dengue and chikungunya viruses are leading causes of emerging mosquito-transmitted (arboviral) disease worldwide. Currently there are no available vaccines or therapeutics making combatting these arboviral diseases one of our most pressing global health challenges. Preliminary evidence shows that glycan recognition is critical for disease immunopathogenesis. This project focuses on the role of viral glycans in arboviral disease with the aim of identifying and expanding on new therapeutic targets