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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 journalArticlepeer-review

Harvard

Gorchakov, AA, Kulemzin, SV, Guselnikov, SV, Baranov, KO, Belovezhets, TN, Mechetina, LV, Volkova, OY, Najakshin, AM, Chikaev, NA, Chikaev, AN, Solodkov, PP, Larichev, VF, Gulyaeva, MA, Markhaev, AG, Kononova, YV, Alekseyev, AY, Shestopalov, AM, Yusubalieva, GM, Klypa, TV, Ivanov, AV, Valuev-Elliston, VT, Baklaushev, VP & Taranin, AV 2021, 'Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern', Cell Discovery, vol. 7, no. 1, 96. https://doi.org/10.1038/s41421-021-00340-8

APA

Gorchakov, A. A., Kulemzin, S. V., Guselnikov, S. V., Baranov, K. O., Belovezhets, T. N., Mechetina, L. V., Volkova, O. Y., Najakshin, A. M., Chikaev, N. A., Chikaev, A. N., Solodkov, P. P., Larichev, V. F., Gulyaeva, M. A., Markhaev, A. G., Kononova, Y. V., Alekseyev, A. Y., Shestopalov, A. M., Yusubalieva, G. M., Klypa, T. V., ... Taranin, A. V. (2021). Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern. Cell Discovery, 7(1), [96]. https://doi.org/10.1038/s41421-021-00340-8

Vancouver

Gorchakov AA, Kulemzin SV, Guselnikov SV, Baranov KO, Belovezhets TN, Mechetina LV et al. Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern. Cell Discovery. 2021 Dec;7(1):96. doi: 10.1038/s41421-021-00340-8

Author

Gorchakov, Andrey A. ; Kulemzin, Sergey V. ; Guselnikov, Sergey V. et al. / Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern. In: Cell Discovery. 2021 ; Vol. 7, No. 1.

BibTeX

@article{a41baee9fd8c4d849625e54b9e0fe0cf,
title = "Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern",
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.",
author = "Gorchakov, {Andrey A.} and Kulemzin, {Sergey V.} and Guselnikov, {Sergey V.} and Baranov, {Konstantin O.} and Belovezhets, {Tatyana N.} and Mechetina, {Ludmila V.} and Volkova, {Olga Yu} and Najakshin, {Alexander M.} and Chikaev, {Nikolai A.} and Chikaev, {Anton N.} and Solodkov, {Pavel P.} and Larichev, {Victor F.} and Gulyaeva, {Marina A.} and Markhaev, {Alexander G.} and Kononova, {Yulia V.} and Alekseyev, {Alexander Yu} and Shestopalov, {Alexander M.} and Yusubalieva, {Gaukhar M.} and Klypa, {Tatiana V.} and Ivanov, {Alexander V.} and Valuev-Elliston, {Vladimir T.} and Baklaushev, {Vladimir P.} and Taranin, {Alexander V.}",
note = "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: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41421-021-00340-8",
language = "English",
volume = "7",
journal = "Cell Discovery",
issn = "2056-5968",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

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