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Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern
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SYSNO ASEP 0557966 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern Author(s) Kováčech, B. (SK)
Fialova, L. (SK)
Filipčík, P. (SK)
Skrabana, R. (SK)
Zilkova, M. (SK)
Paulenka-Ivanovova, N. (SK)
Kovac, A. (SK)
Palova, D. (SK)
Rolkova, G. (SK)
Tomková, K. (CZ)
Csokova, N. (SK)
Markova, K. (SK)
Skrabanova, M. (SK)
Sinska, K. (SK)
Basheer, N. (SK)
Majerova, P. (SK)
Hanes, J. (SK)
Parrak, V. (SK)
Prcina, M. (SK)
Cehlar, O. (SK)
Cente, M. (SK)
Piešťanský, J. (SK)
Fresser, M. (SK)
Novak, M. (CY)
Slávikova, M. (SK)
Borsova, K. (SK)
Čabanová, V. (SK)
Brejová, B. (SK)
Vinař, T. (SK)
Nosek, J. (SK)
Eyer, Luděk (BC-A) RID, ORCID
Hönig, Václav (BC-A) RID, ORCID
Palus, Martin (BC-A) RID, ORCID
Růžek, Daniel (BC-A) RID, ORCID
Vyhlídalová, Tereza (BC-A) ORCID
Straková, Petra (BC-A) ORCID, RID
Mrázková, Blanka (UMG-J)
Zudová, Dagmar (UMG-J)
Koubková, Gizela (UMG-J)
Novosadová, Vendula (UMG-J)
Procházka, Jan (UMG-J) ORCID
Sedláček, Radislav (UMG-J) RID
Žilka, N. (SK)
Kontseková, E. (CZ)Number of authors 45 Article number 103818 Source Title EBioMedicine. - : Elsevier - ISSN 2352-3964
Roč. 76, FEB 2022 (2022)Number of pages 24 s. Publication form Online - E Language eng - English Country GB - United Kingdom Keywords SARS-CoV-2 ; covid-19 ; Neutralizing antibodies ; Escape mutation ; Variants of concern Subject RIV EE - Microbiology, Virology OECD category Virology Subject RIV - cooperation Institute of Molecular Genetics - Microbiology, Virology Method of publishing Open access Institutional support BC-A - RVO:60077344 ; UMG-J - RVO:68378050 UT WOS 000795961100003 EID SCOPUS 85123167401 DOI 10.1016/j.ebiom.2022.103818 Annotation Background The emergence of new SARS-CoV-2 variants of concern B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) that harbor mutations in the viral S protein raised concern about activity of current vaccines and therapeutic antibodies. Independent studies have shown that mutant variants are partially or completely resis-tant against some of the therapeutic antibodies authorized for emergency use. Methods We employed hybridoma technology, ELISA-based and cell-based S-ACE2 interaction assays combined with authentic virus neutralization assays to develop second-generation antibodies, which were specifically selected for their ability to neutralize the new variants of SARS-CoV-2. Findings AX290 and AX677, two monoclonal antibodies with non-overlapping epitopes, exhibit subnanomolar or nanomolar affinities to the receptor binding domain of the viral Spike protein carrying amino acid substitutions N501Y, N439K, E484K, K417N, and a combination N501Y/E484K/K417N found in the circulating virus variants. The antibodies showed excellent neutralization of an authentic SARS-CoV-2 virus representing strains circulating in Europe in spring 2020 and also the variants of concern B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). In addi-tion, AX677 is able to bind Omicron Spike protein just like the wild type Spike. The combination of the two antibodies prevented the appearance of escape mutations of the authentic SARS-CoV-2 virus. Prophylactic administration of AX290 and AX677, either individually or in combination, effectively reduced viral burden and inflammation in the lungs, and prevented disease in a mouse model of SARS-CoV-2 infection. Interpretation The virus-neutralizing properties were fully reproduced in chimeric mouse-human versions of the antibodies, which may represent a promising tool for COVID-19 therapy. Funding The study was funded by AXON Neuroscience SE and AXON COVIDAX a.s. Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2023 Electronic address https://www.sciencedirect.com/science/article/pii/S235239642200007X?via%3Dihub
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