A Novel Conserved Linear Neutralizing Epitope on the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

文献类型： 外文期刊

第一作者： Hua, Rong-Hong

作者： Hua, Rong-Hong;Zhang, Shu-Jian;Niu, Bei;Ge, Jin-Ying;Lan, Ting;Bu, Zhi-Gao

作者机构：

关键词： SARS-CoV-2; spike protein; receptor-binding domain; neutralizing antibody; epitope

期刊名称：MICROBIOLOGY SPECTRUM （ 影响因子：3.7； 五年影响因子：5.9 ）

ISSN： 2165-0497

年卷期： 2023 年 11 卷 4 期

页码：

收录情况： SCI

摘要： The continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it challenging to develop broad-spectrum prophylactic vaccines and therapeutic antibodies. Here, we have identified a broad-spectrum neutralizing antibody and its highly conserved epitope in the receptor-binding domain (RBD) of the spike protein (S) S1 subunit of SARS-CoV-2. First, nine monoclonal antibodies (MAbs) against the RBD or S1 were generated; of these, one RBD-specific MAb, 22.9-1, was selected for its broad RBD-binding abilities and neutralizing activities against SARS-CoV-2 variants. An epitope of 22.9-1 was fine-mapped with overlapping and truncated peptide fusion proteins. The core sequence of the epitope, D-405(N)EVR(S)QIAPGQ(414), was identified on the internal surface of the up-state RBD. The epitope was conserved in nearly all variants of concern of SARS-CoV-2. MAb 22.9-1 and its novel epitope could be beneficial for research on broad-spectrum prophylactic vaccines and therapeutic antibody drugs. The continuous emergence of new variants of SARS-CoV-2 has caused great challenge in vaccine design and therapeutic antibody development. In this study, we selected a broad-spectrum neutralizing mouse monoclonal antibody which recognized a conserved linear B-cell epitope located on the internal surface of RBD. This MAb could neutralize all variants until now. The epitope was conserved in all variants. This work provides new insights in developing broad-spectrum prophylactic vaccines and therapeutic antibodies.

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