Hepatitis C Virus Epitope Immunodominance and B Cell Repertoire Diversity

Abstract

Despite the advent of effective, curative treatments for hepatitis C virus (HCV), a preventative vaccine remains essential for the global elimination of HCV. It is now clear that the induction of broadly neutralising antibodies (bNAbs) is essential for the rational design of such a vaccine. This review details the current understanding of epitopes on the HCV envelope, characterising the potency, breadth and immunodominance of antibodies induced against these epitopes, as well as describing the interactions between B-cell receptors and HCV infection, with a particular focus on bNAb heavy and light chain variable gene usage. Additionally, we consider the importance of a public repertoire for antibodies against HCV, compiling current knowledge and suggesting that further research in this area may be critical to the rational design of an effective HCV vaccine.

Keywords: HCV–BCR interactions; antigenic domains; epitope mapping; hepatitis C virus; human monoclonal antibodies; immunodominance; neutralising antibodies; public antibody repertoire; vaccine development.

Figure 1

Schematic representation of HCV envelope protein E2, developed from the 2013 crystal structure of the protein by Kong et al. The approximate binding residues of nine mAbs covering a range of epitopes is shown. Structural information taken from the Protein Data Bank—accession code 4MWF [18].

Figure 2

Relative immunodominance of Abs specific to antigenic regions (ARs) 1–5 and domains A–E of a GT1 viral envelope (H77) [30].