Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies
Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies
复制标题
针对 SARS-CoV-1 和 SARS-CoV-2 的交叉反应性单克隆抗体的表征：对合理设计和开发泛沙病毒疫苗和中和抗体的启示
DOI：
10.1002/jmv.28440
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发表时间：
2023-02-01
影响因子：
12.7
通讯作者：
Wang，Qiao
中科院分区：
文献类型：
--
作者：
Li，Shibo;Wu，Jianbo;Wang，Qiao
各种流行的SARS-CoV-2变异体（VOC）的出现促进了泛肉瘤病毒疫苗和广泛中和抗体（bNAb）的鉴定。在这里，为了表征针对SARS-CoV-1和SARS-CoV-2的交叉反应性单克隆抗体，并寻找针对所有新出现的SARS-CoV-2的bNAb标准，我们从野生型SARS-CoV-2恢复期供体中分离了几种SARS-CoV-1交叉反应性单克隆抗体（mAb）。这些抗体对各种SARS-CoV-2 VOC表现出广泛的结合能力和交叉中和效力，包括B.1.1.7（Alpha），B.1.351（Beta），P.1（Gamma）和B.1.617.2（Delta），但未能有效中和Omicron变体及其亚系。结构分析揭示了Omicron亚系，而不是其他VOC，如何通过它们的逃逸突变有效地逃避针对SARS-CoV-1的抗体家族交叉反应。对一系列SARS-CoV-1/2交叉反应性bNAb的进一步评估显示，针对SARS-CoV-1和SARS-CoV-2 Omicron变体的中和活性之间呈负相关。总之，这些结果表明，有必要使用针对SARS-CoV-1和SARS-CoV-2 Omicron的交叉中和作为合理设计和开发有效泛肉瘤病毒疫苗和bNAb的标准。
Emergence of various circulating SARS‐CoV‐2 variants of concern (VOCs) promotes the identification of pan‐sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross‐reactive against both SARS‐CoV‐1 and SARS‐CoV‐2 and to search the criterion for bNAbs against all emerging SARS‐CoV‐2, we isolated several SARS‐CoV‐1‐cross‐reactive monoclonal antibodies (mAbs) from a wildtype SARS‐CoV‐2 convalescent donor. These antibodies showed broad binding capacity and cross‐neutralizing potency against various SARS‐CoV‐2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross‐reactive against SARS‐CoV‐1 through their escape mutations. Further evaluation of a series of SARS‐CoV‐1/2‐cross‐reactive bNAbs showed a negative correlation between the neutralizing activities against SARS‐CoV‐1 and SARS‐CoV‐2 Omicron variant. Together, these results suggest the necessity of using cross‐neutralization against SARS‐CoV‐1 and SARS‐CoV‐2 Omicron as criteria for rational design and development of potent pan‐sarbecovirus vaccines and bNAbs.