Publication details

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

Authors	KOVACECH Branislav FIALOVA Lubica FILIPCIK Peter SKRABANA Rostislav ZILKOVA Monika PAULENKA-IVANOVOVA Natalia KOVAC Andrej PALOVA Denisa PAULIKOVA ROLKOVA Gabriela TOMKOVA Katarina TURIC CSOKOVA Natalia MARKOVA Karina SKRABANOVA Michaela SINSKA Kristina BASHEER Neha MAJEROVA Petra HANES Jozef PARRAK Vojtech PRCINA Michal CEHLAR Ondrej CENTE Martin PIESTANSKY Juraj FRESSER Michal NOVAK Michal SLAVIKOVA Monika BORSOVA Kristina CABANOVA Viktoria BREJOVA Bronislava VINAŘ Tomas NOSEK Jozef KLEMPA Boris EYER Luděk HÖNIG Václav PALUS Martin RŮŽEK Daniel VYHLIDALOVA Tereza STRAKOVÁ Petra MRAZKOVA Blanka ZUDOVA Dagmar KOUBKOVA Gizela NOVOSADOVA Vendula PROCHAZKA Jan SEDLACEK Radislav ZILKA Norbert KONTSEKOVA Eva
Year of publication	2022
Type	Article in Periodical
Magazine / Source	EBioMedicine
MU Faculty or unit	Faculty of Science
Citation
Web	https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00007-X/fulltext
Doi	http://dx.doi.org/10.1016/j.ebiom.2022.103818
Keywords	COVID-19; Escape mutation; Neutralizing antibodies; SARS-CoV-2; Variants of concern
Description	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.