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

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.

Basic information

Original name

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

Authors

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 Czech Republic), Václav HÖNIG (203 Czech Republic), Martin PALUS (203 Czech Republic), Daniel RŮŽEK (203 Czech Republic, belonging to the institution), Tereza VYHLIDALOVA, Petra STRAKOVÁ (203 Czech Republic), Blanka MRAZKOVA, Dagmar ZUDOVA, Gizela KOUBKOVA, Vendula NOVOSADOVA, Jan PROCHAZKA, Radislav SEDLACEK, Norbert ZILKA and Eva KONTSEKOVA

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.100

RIV identification code

RIV/00216224:14310/22:00125436

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.ebiom.2022.103818

UT WoS

000795961100003

Keywords in English

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

Abstract

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.

Citovat

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, Václav HÖNIG, Martin PALUS, Daniel RŮŽEK, Tereza VYHLIDALOVA, Petra STRAKOVÁ, Blanka MRAZKOVA, Dagmar ZUDOVA, Gizela KOUBKOVA, Vendula NOVOSADOVA, Jan PROCHAZKA, Radislav SEDLACEK, Norbert ZILKA and Eva KONTSEKOVA. Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern. EBioMedicine. Amsterdam: Elsevier Science BV, 2022, vol. 76, February, p. 1-24. ISSN 2352-3964. Available from: https://dx.doi.org/10.1016/j.ebiom.2022.103818.

@article{1837037,
   author = {Kovacech, Branislav and Fialova, Lubica and Filipcik, Peter and Skrabana, Rostislav and Zilkova, Monika and PaulenkaandIvanovova, Natalia and Kovac, Andrej and Palova, Denisa and Paulikova Rolkova, Gabriela and Tomkova, Katarina and Turic Csokova, Natalia and Markova, Karina and Skrabanova, Michaela and Sinska, Kristina and Basheer, Neha and Majerova, Petra and Hanes, Jozef and Parrak, Vojtech and Prcina, Michal and Cehlar, Ondrej and Cente, Martin and Piestansky, Juraj and Fresser, Michal and Novak, Michal and Slavikova, Monika and Borsova, Kristina and Cabanova, Viktoria and Brejova, Bronislava and Vinař, Tomas and Nosek, Jozef and Klempa, Boris and Eyer, Luděk and Hönig, Václav and Palus, Martin and Růžek, Daniel and Vyhlidalova, Tereza and Straková, Petra and Mrazkova, Blanka and Zudova, Dagmar and Koubkova, Gizela and Novosadova, Vendula and Prochazka, Jan and Sedlacek, Radislav and Zilka, Norbert and Kontsekova, Eva},
   article_location = {Amsterdam},
   article_number = {February},
   doi = {http://dx.doi.org/10.1016/j.ebiom.2022.103818},
   keywords = {COVID-19; Escape mutation; Neutralizing antibodies; SARS-CoV-2; Variants of concern},
   language = {eng},
   issn = {2352-3964},
   journal = {EBioMedicine},
   title = {Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern},
   url = {https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00007-X/fulltext},
   volume = {76},
   year = {2022}
}

TY  - JOUR
ID  - 1837037
AU  - 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
PY  - 2022
TI  - Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern
JF  - EBioMedicine
VL  - 76
IS  - February
SP  - 1-24
EP  - 1-24
PB  - Elsevier Science BV
SN  - 23523964
KW  - COVID-19
KW  - Escape mutation
KW  - Neutralizing antibodies
KW  - SARS-CoV-2
KW  - Variants of concern
UR  - https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00007-X/fulltext
N2  - 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.
ER  -

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, Václav HÖNIG, Martin PALUS, Daniel RŮŽEK, Tereza VYHLIDALOVA, Petra STRAKOVÁ, Blanka MRAZKOVA, Dagmar ZUDOVA, Gizela KOUBKOVA, Vendula NOVOSADOVA, Jan PROCHAZKA, Radislav SEDLACEK, Norbert ZILKA and Eva KONTSEKOVA. Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern. \textit{EBioMedicine}. Amsterdam: Elsevier Science BV, 2022, vol.~76, February, p.~1-24. ISSN~2352-3964. Available from: https://dx.doi.org/10.1016/j.ebiom.2022.103818.

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