Guo Huimin, Jiang Jie, Shen Senlin, Ge Xiangyang, Fan Qing, Zhou Bing, Cheng Lin, Ju Bin, Zhang Zheng
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China.
Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province 518112, China.
iScience. 2023 Apr 21;26(4):106283. doi: 10.1016/j.isci.2023.106283. Epub 2023 Feb 27.
SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with those against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants.
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）奥密克戎BA.2.75亚变体已进化出一系列子代变体，这些子代变体在受体结合域（RBD）携带了几个额外的突变。在此，我们研究了基于BA.2.75的这些单突变是否以及如何影响目前具有明确结构信息的抗RBD单克隆抗体（mAb）的中和作用。约34%的mAb对BA.2.75保持有效的中和活性，这与对BA.2、BA.4/5和BA.2.12.1的中和活性一致。额外的单个R346T、K356T、L452R或F486S突变进一步促使与BA.2.75相关的子代变体在不同程度上逃避广泛中和抗体（bnAb）。只有LY-CoV1404（贝博特韦单抗）对所有测试的奥密克戎亚变体表现出一流的中和效力和广度。总体而言，这些数据明确了病毒逃逸与抗体识别抗原表位之间的联系，这有助于开发针对新出现的SARS-CoV-2变体的下一代通用bnAb。
