Research output: Contribution to journal › Article › peer-review
Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern. / Gorchakov, Andrey A.; Kulemzin, Sergey V.; Guselnikov, Sergey V. et al.
In: Cell Discovery, Vol. 7, No. 1, 96, 12.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern
AU - Gorchakov, Andrey A.
AU - Kulemzin, Sergey V.
AU - Guselnikov, Sergey V.
AU - Baranov, Konstantin O.
AU - Belovezhets, Tatyana N.
AU - Mechetina, Ludmila V.
AU - Volkova, Olga Yu
AU - Najakshin, Alexander M.
AU - Chikaev, Nikolai A.
AU - Chikaev, Anton N.
AU - Solodkov, Pavel P.
AU - Larichev, Victor F.
AU - Gulyaeva, Marina A.
AU - Markhaev, Alexander G.
AU - Kononova, Yulia V.
AU - Alekseyev, Alexander Yu
AU - Shestopalov, Alexander M.
AU - Yusubalieva, Gaukhar M.
AU - Klypa, Tatiana V.
AU - Ivanov, Alexander V.
AU - Valuev-Elliston, Vladimir T.
AU - Baklaushev, Vladimir P.
AU - Taranin, Alexander V.
N1 - Funding Information: Patent applications are being filed for the iB series of nAbs. K.O.B., L.V.M., O.Y.V., A.M.N., N.A.C., and A.V.T. are employees of IMGEN+, LLC. This work was funded by IMGEN+, LLC and several grants listed above. Funding Information: The authors gratefully acknowledge the resources provided by the “Molecular and Cellular Biology” core facility of the IMCB SB RAS, as well as S7 Airlines for their prompt logistics support. We are thankful to our patients, colleagues and friends for their support of the study. A.V.T. was supported by the Russian Fund of Basic Research (RFBR) grant No. 20-04-60527. Development of the modified protocol for single B cell sorting was supported by the RFBR grant No. 18-29-08051 (A.A.G.) and by the Basic scientific research program project No. 0246-2021-0016 (A.V.T.). ELISA experiments were funded by the Russian Ministry of Science and Higher Education of the Russian Federation (agreement 075-15-2019-1660). Publisher Copyright: © 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85117720143&partnerID=8YFLogxK
U2 - 10.1038/s41421-021-00340-8
DO - 10.1038/s41421-021-00340-8
M3 - Article
C2 - 34667147
AN - SCOPUS:85117720143
VL - 7
JO - Cell Discovery
JF - Cell Discovery
SN - 2056-5968
IS - 1
M1 - 96
ER -
ID: 34557815