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鉴定针对 SARS-CoV-1 和 SARS-CoV-2 的交叉反应性单克隆抗体:对泛 SARS-CoV 疫苗和中和抗体的合理设计和开发的启示。

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.

机构信息

Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Fudan University, Shanghai, China.

出版信息

J Med Virol. 2023 Feb;95(2):e28440. doi: 10.1002/jmv.28440.

Abstract

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.

摘要

各种关注的 SARS-CoV-2 变体(VOCs)的出现促进了泛沙贝科病毒疫苗和广泛中和抗体(bNAbs)的鉴定。在这里,为了表征对 SARS-CoV-1 和 SARS-CoV-2 均具有交叉反应性的单克隆抗体,并寻找针对所有新出现的 SARS-CoV-2 的 bNAbs 的标准,我们从野生型 SARS-CoV-2 恢复期供体中分离出几种 SARS-CoV-1 交叉反应性单克隆抗体(mAb)。这些抗体对各种 SARS-CoV-2 VOCs 具有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),但不能有效中和奥密克戎变体及其亚系。结构分析揭示了奥密克戎亚系如何通过逃逸突变有效地逃避针对 SARS-CoV-1 的一种抗体家族交叉反应,而其他 VOCs 则不能。对一系列 SARS-CoV-1/2 交叉反应性 bNAbs 的进一步评估表明,对 SARS-CoV-1 和 SARS-CoV-2 奥密克戎变体的中和活性之间存在负相关。总之,这些结果表明,有必要使用对 SARS-CoV-1 和 SARS-CoV-2 奥密克戎的交叉中和作用作为合理设计和开发有效泛沙贝科病毒疫苗和 bNAbs 的标准。

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