Gorchakov Andrey A, Kulemzin Sergey V, Guselnikov Sergey V, Baranov Konstantin O, Belovezhets Tatyana N, Mechetina Ludmila V, Volkova Olga Yu, Najakshin Alexander M, Chikaev Nikolai A, Chikaev Anton N, Solodkov Pavel P, Larichev Victor F, Gulyaeva Marina A, Markhaev Alexander G, Kononova Yulia V, Alekseyev Alexander Yu, Shestopalov Alexander M, Yusubalieva Gaukhar M, Klypa Tatiana V, Ivanov Alexander V, Valuev-Elliston Vladimir T, Baklaushev Vladimir P, Taranin Alexander V
Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Novosibirsk State University, Novosibirsk, Russia.
Cell Discov. 2021 Oct 19;7(1):96. doi: 10.1038/s41421-021-00340-8.
In the absence of virus-targeting small-molecule drugs approved for the treatment and prevention of COVID-19, broadening the repertoire of potent SARS-CoV-2-neutralizing antibodies represents an important area of research in response to the ongoing pandemic. Systematic analysis of such antibodies and their combinations can be particularly instrumental for identification of candidates that may prove resistant to the emerging viral escape variants. Here, we isolated a panel of 23 RBD-specific human monoclonal antibodies from the B cells of convalescent patients. A surprisingly large proportion of such antibodies displayed potent virus-neutralizing activity both in vitro and in vivo. Four of the isolated nAbs can be categorized as ultrapotent with an apparent IC below 16 ng/mL. We show that individual nAbs as well as dual combinations thereof retain activity against currently circulating SARS-CoV-2 variants of concern (such as B.1.1.7, B.1.351, B.1.617, and C.37), as well as against other viral variants. When used as a prophylactics or therapeutics, these nAbs could potently suppress viral replication and prevent lung pathology in SARS-CoV-2-infected hamsters. Our data contribute to the rational development of oligoclonal therapeutic nAb cocktails mitigating the risk of SARS-CoV-2 escape.
在缺乏已批准用于治疗和预防COVID-19的靶向病毒小分子药物的情况下，扩大强效严重急性呼吸综合征冠状病毒2（SARS-CoV-2）中和抗体的种类是应对当前大流行的一个重要研究领域。对这类抗体及其组合进行系统分析，对于鉴定可能对新出现的病毒逃逸变体具有抗性的候选抗体尤为有用。在此，我们从康复患者的B细胞中分离出一组23种RBD特异性人单克隆抗体。这类抗体中，有相当大比例在体外和体内均表现出强效的病毒中和活性。所分离的四种中和抗体（nAbs）可归类为超强效，其表观半数抑制浓度（IC）低于16 ng/mL。我们表明，单个nAb及其双重组合对目前正在传播的SARS-CoV-2变异株（如B.1.1.7、B.1.351、B.1.617和C.37）以及其他病毒变体均保持活性。当用作预防或治疗药物时，这些nAb可有效抑制SARS-CoV-2感染仓鼠体内的病毒复制并预防肺部病变。我们的数据有助于合理开发寡克隆治疗性nAb鸡尾酒，降低SARS-CoV-2逃逸风险。
