Hepatitis C virus contributes to aggravation of the immunosuppressive environment by increasing the suppressive activity of natural regulatory T cells

Methods: A soluble form of E2 protein (sE2) derived from the HCV/Con1 strain was produced at high levels, up to 100mg/L, in stably transfected Drosophila S2 cell culture. This sE2 protein could bind to HCV receptors CD81 and SRB1, block cell-culture-derived HCV (HCVcc) infection, and react with known broadly neutralising monoclonal antibodies. Findings: Immunisation studies showed that sE2 was able to induce production of serum antibodies neutralising HCVcc of all seven genotypes in mice, rabbits, and rhesus macaques. Additionally, sE2-immunised macaques developed systemic and intra-hepatic memory T cells specific for E2. In-vivo challenge and protection studies are ongoing to determinewhether such neutralisation is sufficient to prevent HCV infection in mice. Interpretation: These data show that sE2 is a promising HCV vaccine candidate that warrants further preclinical and clinical development.