Branislav Kovacech, Lubica Fialova, Peter Filipcik, Rostislav Skrabana, Monika Zilkova, Natalia Paulenka-Ivanovova, Andrej Kovac, Denisa Palova, Gabriela Paulikova Rolkova, Katarina Tomkova, Natalia Turic Csokova, Karina Markova, Michaela Skrabanova, Kristina Sinska, Neha Basheer, Petra Majerova, Jozef Hanes, Vojtech Parrak, Michal Prcina, Ondrej Cehlar, Martin Cente, Juraj Piestansky, Michal Fresser, Michal Novak, Monika Slavikova, Kristina Borsova, Viktoria Cabanova, Bronislava Brejova, Tomas Vinar, Jozef Nosek, Boris Klempa, Ludek Eyer, Vaclav Honig, Martin Palus, Daniel Ruzek, Tereza Vyhlidalova, Petra Strakova, Blanka Mrazkova, Dagmar Zudova, Gizela Koubkova, Vendula Novosadova, Jan Prochazka, Radislav Sedlacek, Norbert Zilka, Eva Kontsekova. Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern. EBioMedicine, 76:103818. 2022.
Download preprint: not available
Download from publisher: https://doi.org/10.1016/j.ebiom.2022.103818
Related web page: not available
Bibliography entry: BibTeX
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.