Molecular analysis of a public cross-neutralizing antibody response to SARS-CoV-2.
Molecular analysis of a public cross-neutralizing antibody response to SARS-CoV-2.
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对 SARS-CoV-2 公共交叉中和抗体反应的分子分析。
DOI：
10.1101/2022.05.17.492220
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Wu,NicholasC
中科院分区：
文献类型：
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作者：
Yuan,Meng;Wang,Yiquan;Lv,Huibin;Wilson,IanA;Wu,NicholasC
随着严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）变异体（VOC）的不断出现，交叉中和抗体反应成为下一代设计更通用的COVID-19疫苗的关键。通过分析文献中已发表的数据，我们在这里报告说，生殖系基因IGHV 2 -5/IGLV 2 -14的组合代表了对受体结合结构域（RBD）的公共抗体应答，该受体结合结构域有效地交叉中和了广泛的VOC，包括Omicron及其亚系。详细的分子分析表明，IGHV 2 -5/IGLV 2 -14编码的RBD抗体的互补决定区H3序列具有优选的11个氨基酸的长度和保守的HxIxxI基序。此外，这些抗体由于位于互补位的IGHV 2 -5的氨基酸残基54处的等位基因多态性而具有强的等位基因偏好。这些发现对于理解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COVID-19疫苗的开发具有重要意义。
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.