Počet záznamů: 1
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 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern Tvůrce(i) 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)Celkový počet autorů 45 Číslo článku 103818 Zdroj.dok. EBioMedicine. - : Elsevier - ISSN 2352-3964
Roč. 76, FEB 2022 (2022)Poč.str. 24 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova SARS-CoV-2 ; covid-19 ; Neutralizing antibodies ; Escape mutation ; Variants of concern Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Virology Vědní obor RIV – spolupráce Ústav molekulární genetiky - Mikrobiologie, virologie Způsob publikování Open access Institucionální podpora BC-A - RVO:60077344 ; UMG-J - RVO:68378050 UT WOS 000795961100003 EID SCOPUS 85123167401 DOI 10.1016/j.ebiom.2022.103818 Anotace 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/) Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2023 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S235239642200007X?via%3Dihub
Počet záznamů: 1