Antigenicity of key hepatitis C virus E1E2 glycoprotein neutralizing sites is genotype independent

The development of an effective prophylactic hepatitis C virus (HCV) vaccine is a priority to achieve global elimination of the virus. Accurate assessment of the neutralizing breadth of antibodies induced by vaccines and a clear understanding of the antigenic differences between viral variants included in vaccines are both critical for vaccine development. Prior studies have indicated that HCV genotypes (gts) do not dictate the sensitivity of HCV envelope glycoprotein (E1E2) variants to neutralizing antibodies. However, most of these prior studies under-sampled variants from gts 2–6. Here, we selected a genetically diverse and representative panel of gt 2–6 E1E2 variants, used them to generate HCV pseudoparticles (HCVpp), and measured neutralization of these HCVpp by neutralizing antibodies and HCV-immune plasma from persons infected with gt 1–6 viruses. We found that neutralization results obtained with this gt 2–6 panel were remarkably similar to results obtained with a previously described, antigenically diverse, gt 1-predominant reference panel of 15 HCVpp. These data confirm that, even considering genetically diverse HCV variants across gt 1–6, E1E2 antigenicity is not dictated by gt, and that the previously published panel of 15 HCVpp represents neutralization of all HCV gts with reasonable accuracy.