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
UNDERSTANDING HEPATITIS C VIRUS-SPECIFIC T CELL TOLERANCE
Funder
National Health and Medical Research Council
Funding Amount
$429,710.00
Summary
Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have ....Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have the effect of inhibiting the immune response and result in the outcome that we currently recognise as persistent HCV infection.Read moreRead less
Current anti-HIV therapies can't cure HIV because HIV remains silent(latent) in long-lived cells. The HIV life cycle and virus production is linked to activation of the host cell, which is regulated by dendritic cells. This grant will explore how the factors controlling T cell activation and proliferation control virus expression and latency. By understanding how latent infection is established and maintained, these studies will potentially identify new ways to eliminate HIV infection.
Herpesviruses infect us all and cause cancer, blindness, and congenital disability. Developing vaccines requires information from both patients and experimental animals. CD4 T cells seem to suppress directly virus replication, and cells in the nose provide an important way for herpesviruses to get in. We will test whether CD4 T cells can clear nasal infection; what targets they recognize; and how they act. Thus we can establish whether CD4 T cell-directed vaccines might protect against disease.
Mechanisms By Which Varicella Zoster Virus And Herpes Simplex Virus Control Host Functions To Enhance Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$631,999.00
Summary
Varicella Zoster Virus and Herpes Simplex Virus are alpha-herpesviruses that cause diseases in a majority of the human population. This proposal will explore issues fundamental to disease and pathogenesis of these two closely related herpesviruses, focusing on how these viruses can control host function. In particular, we will define the interactions between these viruses and the natural killer (NK) cell response.
The Role Of Paramyxovirus P Protein Subcellular Trafficking In Virus Pathogenicity And Antagonism Of Host Interferon Responses
Funder
National Health and Medical Research Council
Funding Amount
$78,491.00
Summary
Emerging zoonotic viruses pose a major health threat worldwide, highlighted by recent outbreaks of viruses such as Nipah and Hendra via interspecies invasion to infect humans. A major barrier to interspecies infection is the innate immune response, which viruses must evolve to combat before successful infection can occur. We aim to examine in detail the mechanisms underlying immune evasion of such viruses, with the ultimate goal of discovering novel targets for therapeutics to viral infection.
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.