Speaker
Description
Introduction: An effective hepatitis C virus (HCV) vaccine must induce broadly neutralising antibodies (bnAbs) to provide protection against its high diversity. Unfortunately, there has yet to be a successful HCV vaccine that is capable of inducing bnAbs across multiple recipients. A more comprehensive understanding of the impact of viral factors, such as the properties of the infecting HCV variant with the host antibody response is clearly required. If HCV shares a similar capacity with HIV-1 and SARS-CoV-2, to imprint antibody responses across multiple individuals, identification of specific viral variants that imprint bnAbs could inform the development of more effective HCV vaccine immunogens.
Methods: In this study, the viral sequences from 1,075 HCV infected individuals from four NSW HCV infected cohorts were aligned and a genetic distance matrix was generated to identify 38 transmission clusters of individuals infected by highly similar viruses. ELISAs were used to assess antibody binding and epitope mapping, and pseudoparticle assays were used to measure antibody neutralisation breadth. Correlation analysis was performed to determine if these antibody responses correlated within members of the same transmission clusters.
Results: This study found significant correlation within HCV transmission clusters for antibody binding magnitude and epitope specificity for five of the seven epitopes tested. The neutralisation potency and breadth varied within transmission clusters, and correlation of neutralisation potency within transmission clusters was only observed for HCV pseudoparticles known to be more neutralisation resistant. This study was also able to identify specific HCV variants that were capable of inducing bnAbs across multiple individuals.
Discussion: These findings demonstrate that different variants of HCV have varying capacity to imprint antibody responses across individuals. Application of this knowledge of HCV antibody imprinting to vaccine design may allow for the identification of immunogens able to consistently induce bnAbs between individuals.
