Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern

0557966 - BC 2023 RIV GB eng J - Journal Article
Kováčech, B. - Fialova, L. - Filipčík, P. - Skrabana, R. - Zilkova, M. - Paulenka-Ivanovova, N. - Kovac, A. - Palova, D. - Rolkova, G. - Tomková, K. - Csokova, N. - Markova, K. - Skrabanova, M. - Sinska, K. - Basheer, N. - Majerova, P. - Hanes, J. - Parrak, V. - Prcina, M. - Cehlar, O. - Cente, M. - Piešťanský, J. - Fresser, M. - Novak, M. - Slávikova, M. - Borsova, K. - Čabanová, V. - Brejová, B. - Vinař, T. - Nosek, J. - Eyer, Luděk - Hönig, Václav - Palus, Martin - Růžek, Daniel - Vyhlídalová, Tereza - Straková, Petra - Mrázková, Blanka - Zudová, Dagmar - Koubková, Gizela - Novosadová, Vendula - Procházka, Jan - Sedláček, Radislav - Žilka, N. - Kontseková, E. … Total 45 authors
Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern.
EBioMedicine. Roč. 76, FEB 2022 (2022), č. článku 103818. ISSN 2352-3964. E-ISSN 2352-3964
Institutional support: RVO:60077344 ; RVO:68378050
Keywords : SARS-CoV-2 * covid-19 * Neutralizing antibodies * Escape mutation * Variants of concern
OECD category: Virology; Virology (UMG-J)
Impact factor: 11.1, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S235239642200007X?via%3Dihub

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/)
Permanent Link: https://hdl.handle.net/11104/0334892