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

EBioMedicine

Peter Filipcik¹  Neha Basheer²  Dagmar Zudova²  Rostislav Skrabana²  Petra Strakova²  Gabriela Paulikova Rolkova²  Michal Prcina²  Vendula Novosadova²  Jozef Hanes²  Michaela Skrabanova²  Daniel Ruzek²  Martin Cente²  Boris Klempa²  Eva Kontsekova²  Lubica Fialova²  Andrej Kovac²  Michal Fresser²  Monika Slavikova²  Tomas Vinař²  Vaclav Hönig³  Radislav Sedlacek³  Natalia Turic Csokova³  Viktoria Cabanova³  Monika Zilkova⁴  Jan Prochazka⁵  Ludek Eyer⁵  Katarina Tomkova⁵  Branislav Kovacech⁶  Natalia Paulenka-Ivanovova⁷  Karina Markova⁷  Norbert Zilka⁷  Vojtech Parrak⁷  Jozef Nosek⁷  Tereza Vyhlidalova⁷  Juraj Piestansky⁷  Michal Novak⁷  Kristina Sinska⁷  Ondrej Cehlar⁷  Martin Palus⁷  Denisa Palova⁷  Bronislava Brejova⁷  Blanka Mrazkova⁷  Gizela Koubkova⁷  Petra Majerova⁷  Kristina Borsova⁸ 

[1] AXON Neuroscience R&D Services SE;Bratislava, 811 02, Slovakia;Bratislava, 845 10, Slovakia;Corresponding authors: Branislav Kovacech, PhD and Norbert Zilka, PhD, AXON Neuroscience R&D Services SE, Dvorakovo nabrezie 11, 811 02, Bratislava, Slovakia. Tel: [phone].;Institute of Neuroimmunology, Slovak Academy of Sciences;AXON COVIDAX a. s.;AXON Neuroscience R&D Services SE;Institute of Neuroimmunology, Slovak Academy of Sciences;

关键词: SARS-CoV-2;    COVID-19;    Neutralizing antibodies;    Escape mutation;    Variants of concern;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: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 resistant 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 addition, 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.

【 授权许可】

Unknown