B cell response to HCV infection

Injecting drug use and the sharing of contaminated equipment represents a major driver of the Hepatitis C virus (HCV) pandemic. As a result, people who inject drugs (PWID) are at constant risk of infection and reinfection.

In a longitudinal study of PWID we have identified three individuals who possess high titres of broadly neutralising antibodies (brNAbs).

Notably, they do not possess characteristic specificities associated with brNAbs isolated from chronically infected patients in that their sera do not block E2-CD81 interactions and are not directed to two major antigenic regions.

Two of the three individuals have not developed chronic HCV for almost 10 years despite regular episodes of re-exposure, while the third remained free of chronic disease for the five years that they were enrolled in the study.

We hypothesise that long-term protection from chronic HCV in these individuals is associated with elicitation of unique protective NAb specificities.

We will:

  • Define the antibody signature in the immune serum of protected individuals
  • Mine the B cell repertoire to identify novel IgG specificities that confer broad neutralisation.
  • Define the epitopes of mined IgGs and their mechanism of neutralisation.
  • Examine whether these mined IgGs can control HCV replication and prevent neutralisation escape.

This information will be used to inform prophylactic vaccine design to favour the elicitation of protective antibody specificities.

Commonly used techniques include virus infection, western blotting, affinity purification, protein expression, ELISA, receptor binding assays, antibody neutralisation assays, RNA transcription and transfection, gene cloning and expression, DNA sequencing, and FACS.

Health Issue

Contact Details

For any general enquiries relating to this project, please contact:

Professor Heidi E Drummer

Program Director, Disease Elimination; Co-Head, Drummer/Poumbourios Laboratory