RT Journal Article
SR Electronic
T1 Second-Generation Antibodies Neutralize Emerging SARS-CoV-2 Variants of Concern
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.09.447527
DO 10.1101/2021.06.09.447527
A1 Branislav Kovacech
A1 Lubica Fialova
A1 Peter Filipcik
A1 Rostislav Skrabana
A1 Monika Zilkova
A1 Natalia Paulenka-Ivanovova
A1 Andrej Kovac
A1 Denisa Palova
A1 Gabriela Paulíkova Rolkova
A1 Katarina Tomkova
A1 Natalia Turic Csokova
A1 Karina Markova
A1 Michaela Skrabanova
A1 Kristina Sinska
A1 Neha Basheer
A1 Petra Majerova
A1 Jozef Hanes
A1 Vojtech Parrak
A1 Michal Prcina
A1 Ondrej Cehlar
A1 Martin Cente
A1 Juraj Piestansky
A1 Michal Fresser
A1 Michal Novak
A1 Monika Slavikova
A1 Kristina Borsova
A1 Viktoria Cabanova
A1 Bronislava Brejova
A1 Tomas Vinař
A1 Jozef Nosek
A1 Boris Klempa
A1 Norbert Zilka
A1 Eva Kontsekova
YR 2021
UL http://biorxiv.org/content/early/2021/06/09/2021.06.09.447527.abstract
AB Recently emerged SARS-CoV-2 variants show resistance to some antibodies that were authorized for emergency use. We employed hybridoma technology combined with authentic virus assays to develop second-generation antibodies, which were specifically selected for their ability to neutralize new variants of SARS-CoV-2. 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 and B.1.351. Finally, the combination of the two antibodies prevented the appearance of escape mutations of the authentic SARS-CoV-2 virus. The neutralizing properties were fully reproduced in chimeric mouse-human versions, which may represent a promising tool for COVID-19 therapy.Competing Interest Statementll authors affiliated with AXON COVIDAX a.s., AXON Neuroscience SE, AXON Neuroscience R#x0026;D Services SE (BKo, LF, PF, RS, MZ, NP-I, AK, DP, GPR, KT, NTC, KM, PM, VP, KS, NB, JH, MP, MC, JP, MF, MN, NZ, EK) receive a salary from the respective companies. MS, OC, KB, VC, BB, TV, and JN have no conflict of interest. MS and BKl have received personal payments for plaque reduction neutralization studies.