Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Cell Rep. 2022 Nov 15;41(7):111650. doi: 10.1016/j.celrep.2022.111650. Epub 2022 Oct 27.
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns (VOCs) continue to emerge, cross-neutralizing antibody responses become key toward next-generation design of a more universal COVID-19 vaccine. By analyzing published data from the literature, we report here that the combination of germline genes IGHV2-5/IGLV2-14 represents a public antibody response to the receptor-binding domain (RBD) that potently cross-neutralizes a broad range of VOCs, including Omicron and its sub-lineages. Detailed molecular analysis shows that the complementarity-determining region H3 sequences of IGHV2-5/IGLV2-14-encoded RBD antibodies have a preferred length of 11 amino acids and a conserved HxIxxI motif. In addition, these antibodies have a strong allelic preference due to an allelic polymorphism at amino acid residue 54 of IGHV2-5, which is located at the paratope. These findings have important implications for understanding cross-neutralizing antibody responses to SARS-CoV-2 and its heterogenicity at the population level as well as the development of a universal COVID-19 vaccine.
随着严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变体的不断出现，中和抗体的反应成为下一代更通用的 COVID-19 疫苗设计的关键。通过分析文献中已发表的数据，我们在此报告，种系基因IGHV2-5/IGLV2-14 的组合代表了针对受体结合域（RBD）的公共抗体反应，能够有效地中和广泛的变体，包括奥密克戎及其亚系。详细的分子分析表明，IGHV2-5/IGLV2-14 编码的 RBD 抗体的互补决定区 H3 序列具有 11 个氨基酸的优选长度和保守的 HxIxxI 基序。此外，由于IGHV2-5 残基 54 处的等位基因多态性，这些抗体具有强烈的等位基因偏好性，该残基位于表位。这些发现对于理解 SARS-CoV-2 的中和抗体反应及其在人群水平上的异质性以及通用 COVID-19 疫苗的开发具有重要意义。
