Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern

Andrey A Gorchakov; Sergey V Kulemzin; Sergey V Guselnikov; Konstantin O Baranov; Tatyana N Belovezhets; Ludmila V Mechetina; Olga Yu Volkova; Alexander M Najakshin; Nikolai A Chikaev; Anton N Chikaev; Pavel P Solodkov; Victor F Larichev; Marina A Gulyaeva; Alexander G Markhaev; Yulia V Kononova; Alexander Yu Alekseyev; Alexander M Shestopalov; Gaukhar M Yusubalieva; Tatiana V Klypa; Alexander V Ivanov; Vladimir T Valuev-Elliston; Vladimir P Baklaushev; Alexander V Taranin

doi:10.1038/s41421-021-00340-8

Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern

Cell Discov. 2021 Oct 19;7(1):96. doi: 10.1038/s41421-021-00340-8.

Authors

Andrey A Gorchakov^#¹, Sergey V Kulemzin^#¹, Sergey V Guselnikov^#¹, Konstantin O Baranov^#¹, Tatyana N Belovezhets¹, Ludmila V Mechetina^{1

2}, Olga Yu Volkova¹, Alexander M Najakshin¹, Nikolai A Chikaev¹, Anton N Chikaev¹, Pavel P Solodkov¹, Victor F Larichev³, Marina A Gulyaeva^{2

4}, Alexander G Markhaev⁴, Yulia V Kononova⁴, Alexander Yu Alekseyev^{4

5}, Alexander M Shestopalov^{4

5}, Gaukhar M Yusubalieva⁶, Tatiana V Klypa⁶, Alexander V Ivanov⁷, Vladimir T Valuev-Elliston⁷, Vladimir P Baklaushev⁶, Alexander V Taranin⁸

Affiliations

¹ Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
² Novosibirsk State University, Novosibirsk, Russia.
³ National Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, Moscow, Russia.
⁴ Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia.
⁵ Dagestan State University, Makhachkala, Republic of Dagestan, Russia.
⁶ Federal Research and Clinical Center for Specialized Medical Care, FMBA of Russia, Moscow, Russia.
⁷ Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
⁸ Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia. taranin@mcb.nsc.ru.

^# Contributed equally.

Abstract

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 IC₁₀₀ 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.