Featured publication
March 2026
The development of an effective hepatitis C virus (HCV) vaccine requires reliable tools to measure the neutralizing breadth of antibody responses. A widely used reference panel of 15 HCV pseudoparticles (HCVpp) exists, but it is dominated by genotype (gt) 1 variants, raising concern that it may not fully represent global HCV diversity.
This recent study, performed in collaboration with groups in the USA, evaluated whether the neutralization sensitivity of E1E2 glycoproteins differs across HCV genotypes 2–6 and whether these differences require updating the current reference viruses commonly used for studies of vaccine efficacy. This develops and expands studies performed by members of the OneVirology group.
The main findings of the study were that Genetic diversity of HCV does not correlate with antigenic diversity. Despite wide sequence variation among genotypes 2–6, the functional antigenicity of the 12 new HCVpp variants was highly similar to that of the original reference panel. The 12 variants tested displayed a full range of neutralization sensitivity (Tier 1–4), closely mirroring the distribution in the current reference panel. Neutralization by human plasma displays similar patterns across different panels of viruses. Plasma derived from individuals infected with genotypes 1–5 neutralized both panels similarly. Importantly, in experiments with plasma from infections representing Genotype 6, the new panel exhibited slightly higher resistance compared to the reference panel—suggesting genotype 6 infections may induce antibodies targeting partially distinct epitopes. Overall, the antigenic properties of E1E2 glycoproteins are not dictated by viral genotype, and the existing 15‑variant reference HCVpp panel provide a useful tool for vaccine development and neutralization breadth assessment.
This recent study, performed in collaboration with groups in the USA, evaluated whether the neutralization sensitivity of E1E2 glycoproteins differs across HCV genotypes 2–6 and whether these differences require updating the current reference viruses commonly used for studies of vaccine efficacy. This develops and expands studies performed by members of the OneVirology group.
The main findings of the study were that Genetic diversity of HCV does not correlate with antigenic diversity. Despite wide sequence variation among genotypes 2–6, the functional antigenicity of the 12 new HCVpp variants was highly similar to that of the original reference panel. The 12 variants tested displayed a full range of neutralization sensitivity (Tier 1–4), closely mirroring the distribution in the current reference panel. Neutralization by human plasma displays similar patterns across different panels of viruses. Plasma derived from individuals infected with genotypes 1–5 neutralized both panels similarly. Importantly, in experiments with plasma from infections representing Genotype 6, the new panel exhibited slightly higher resistance compared to the reference panel—suggesting genotype 6 infections may induce antibodies targeting partially distinct epitopes. Overall, the antigenic properties of E1E2 glycoproteins are not dictated by viral genotype, and the existing 15‑variant reference HCVpp panel provide a useful tool for vaccine development and neutralization breadth assessment.