ArticleFrontiers in immunology2026
Hepatitis C virus E1 protein-specific linear B-cell epitopes, pan-genotype reactivity, and functional relevance.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Hepatitis C virus (HCV) infection poses a major global risk for chronic liver disease, underscoring the critical need for prevention. Our previous studies demonstrated that HCV-modified soluble E1/E2 Methods: Analyses for the evaluation of linear B-cell epitopes, specifically antibody elicitation by genotype 1a E1 mRNA-LNP immunization, were performed using a panel of E1 overlapping peptides. HCV pseudotype neutralization, interruption by antibody binding to epitope regions, and association between E1/E2 were biochemically analyzed for the impairment of known E2 receptor-binding functions, including surrogate virus neutralization. Results: Binding inhibition-based ELISA identified peptides having a distinct reactivity pattern of immune mouse sera, revealing four linear regions (Groups A-D). One of the peptides (Group A, P1) corresponded to an antigenic region previously characterized as a key linear B-cell epitope. HCV pseudotype neutralization assay using rabbit anti-P1 peptide serum demonstrated multi-HCV genotype neutralization. The relatively conserved linear B-cell epitope was found to localize in the α1 helix region, closer to the N-terminal ectodomain of E1/E2 major receptor-binding area. However, a much-conserved P2 epitope (Group D), with residues reported to interplay with the tight junction protein claudin-1 and scavenger receptor B type I, induced a detectable HCV pseudotype neutralization. Interruption by antibody binding to the P1 and P2 regions may impair intimate association between E1/E2, leading to the impairment of known E2 receptor-binding functions, including virus neutralization activity. Surface plasmon resonance suggested similar antibody binding affinity of the two rabbit antibodies (~10 Conclusions: Collectively, the findings identified novel B-cell epitopes of E1 glycoprotein cross-reactive among HCV genotypes and may serve as a promising candidate to include for a rational design of a pan-genotypic HCV vaccine.
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