Cowton Vanessa M, Owsianka Ania M, Fadda Valeria, Ortega-Prieto Ana Maria, Cole Sarah J, Potter Jane A, Skelton Jessica K, Jeffrey Nathan, Di Lorenzo Caterina, Dorner Marcus, Taylor Garry L, Patel Arvind H
MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow, UK.
Biomedical Sciences Research Complex, University of St. Andrews, Fife, UK.
NPJ Vaccines. 2021 Jan 8;6(1):7. doi: 10.1038/s41541-020-00269-1.
HCV vaccine development is stymied by the high genetic diversity of the virus and the variability of the envelope glycoproteins. One strategy to overcome this is to identify conserved, functionally important regions-such as the epitopes of broadly neutralizing antibodies (bNAbs)-and use these as a basis for structure-based vaccine design. Here, we report an anti-idiotype approach that has generated an antibody that mimics a highly conserved neutralizing epitope on HCV E2. Crucially, a mutagenesis screen was used to identify the antibody, designated B2.1 A, whose binding characteristics to the bNAb AP33 closely resemble those of the original antigen. Protein crystallography confirmed that B2.1 A is a structural mimic of the AP33 epitope. When used as an immunogen B2.1 A induced antibodies that recognized the same epitope and E2 residues as AP33 and most importantly protected against HCV challenge in a mouse model.
丙型肝炎病毒（HCV）疫苗的研发因该病毒的高度基因多样性和包膜糖蛋白的变异性而受阻。克服这一问题的一种策略是识别保守的、具有重要功能的区域，如广泛中和抗体（bNAbs）的表位，并以此为基础进行基于结构的疫苗设计。在此，我们报告一种抗独特型方法，该方法产生了一种模拟HCV E2上高度保守中和表位的抗体。至关重要的是，通过诱变筛选鉴定出了名为B2.1 A的抗体，其与bNAb AP33的结合特性与原始抗原极为相似。蛋白质晶体学证实B2.1 A是AP33表位的结构模拟物。当用作免疫原时，B2.1 A诱导产生的抗体能识别与AP33相同的表位和E2残基，最重要的是，在小鼠模型中能保护机体免受HCV攻击。
