Yuan Meng, Wang Yiquan, Lv Huibin, Wilson Ian A, Wu Nicholas C
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.
bioRxiv. 2022 May 18:2022.05.17.492220. doi: 10.1101/2022.05.17.492220.
As SARS-CoV-2 variants of concerns (VOCs) continue to emerge, cross-neutralizing antibody responses become key towards 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 all VOCs to date, 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 locates 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）变异株（VOCs）不断出现，交叉中和抗体反应成为下一代更通用的新冠疫苗设计的关键。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的组合代表了对受体结合域（RBD）的一种公共抗体反应，该反应能有效交叉中和迄今为止所有的VOCs，包括奥密克戎及其亚谱系。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氨基酸残基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，该残基位于抗原结合部位。这些发现对于理解针对SARS-CoV-2的交叉中和抗体反应及其在人群水平的异质性以及通用新冠疫苗的开发具有重要意义。
