J 2022

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

KOVACECH, Branislav; Lubica FIALOVA; Peter FILIPCIK; Rostislav SKRABANA; Monika ZILKOVA et. al.

Základní údaje

Originální název

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

Autoři

KOVACECH, Branislav; 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 VINAŘ; Jozef NOSEK; Boris KLEMPA; Luděk EYER (203 Česká republika); Václav HÖNIG (203 Česká republika); Martin PALUS (203 Česká republika); Daniel RŮŽEK (203 Česká republika, domácí); Tereza VYHLIDALOVA; Petra STRAKOVÁ (203 Česká republika); Blanka MRAZKOVA; Dagmar ZUDOVA; Gizela KOUBKOVA; Vendula NOVOSADOVA; Jan PROCHAZKA; Radislav SEDLACEK; Norbert ZILKA a Eva KONTSEKOVA

Vydání

EBioMedicine, Amsterdam, Elsevier Science BV, 2022, 2352-3964

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 11.100

Kód RIV

RIV/00216224:14310/22:00125436

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000795961100003

EID Scopus

2-s2.0-85123167401

Klíčová slova anglicky

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

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 20. 6. 2022 15:27, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

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.