Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Adimab, LLC, Lebanon, NH, USA.
Commun Biol. 2022 Jul 29;5(1):766. doi: 10.1038/s42003-022-03700-6.
Studying the antibody response to SARS-CoV-2 informs on how the human immune system can respond to antigenic variants as well as other SARS-related viruses. Here, we structurally identified a YYDRxG motif encoded by IGHD3-22 in CDR H3 that facilitates antibody targeting to a functionally conserved epitope on the SARS-CoV-2 receptor binding domain. A computational search for a YYDRxG pattern in publicly available sequences uncovered 100 such antibodies, many of which can neutralize SARS-CoV-2 variants and SARS-CoV. Thus, the YYDRxG motif represents a common convergent solution for the human humoral immune system to target sarbecoviruses including the Omicron variant. These findings suggest an epitope-targeting strategy to identify potent and broadly neutralizing antibodies for design of pan-sarbecovirus vaccines and antibody therapeutics.
研究针对 SARS-CoV-2 的抗体反应可以了解人体免疫系统如何针对抗原变体以及其他 SARS 相关病毒做出反应。在这里，我们在 CDR H3 中鉴定出由 IGHD3-22 编码的 YYDRxG 基序，该基序有助于抗体针对 SARS-CoV-2 受体结合域上功能保守表位的靶向。在公开可用的序列中进行的计算搜索发现了 100 种这样的抗体，其中许多可以中和 SARS-CoV-2 变体和 SARS-CoV。因此，YYDRxG 基序代表了人类体液免疫系统针对包括奥密克戎变体在内的 sarbecovirus 的共同趋同解决方案。这些发现表明了一种针对表位的策略，可以识别有效的、广泛中和的抗体，用于设计泛 sarbecovirus 疫苗和抗体疗法。
