State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases/Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (Shantou University and University of Hong Kong), Shantou University, Shantou 515063, China.
Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2204256119. doi: 10.1073/pnas.2204256119. Epub 2022 Aug 16.
Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.
用于治疗 COVID-19 的抗体疗法取得了巨大成功。然而，最近奥密克戎变异株的出现带来了挑战，因为它逃避了大多数现有 SARS-CoV-2 中和抗体（nAb）的检测。在这里，我们通过连续免疫两种假病毒成功地产生了一组 SARS-CoV-2/SARS-CoV 交叉中和抗体。在潜在的候选物中，我们发现 nAb X01、X10 和 X17 对大多数关注的变体具有广泛的中和潜力，进一步鉴定 X17 是一种 5 类 nAb，对奥密克戎变体的中和作用没有减弱。三种抗体与原型 SARS-CoV、SARS-CoV-2 和 Delta 和奥密克戎变体的刺突蛋白复合物的低温电子显微镜结构定义了受体结合域上三个非重叠的保守表位。三抗体混合物表现出增强的抗病毒逃逸能力，并有效保护仓鼠免受 Beta 变体的感染。我们的发现将有助于开发针对 SARS-CoV-2 及其新兴变体的抗体疗法和广谱疫苗。
