Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern
Summary: 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...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Branislav Kovacech [verfasserIn] Lubica Fialova [verfasserIn] Peter Filipcik [verfasserIn] Rostislav Skrabana [verfasserIn] Monika Zilkova [verfasserIn] Natalia Paulenka-Ivanovova [verfasserIn] Andrej Kovac [verfasserIn] Denisa Palova [verfasserIn] Gabriela Paulikova Rolkova [verfasserIn] Katarina Tomkova [verfasserIn] Natalia Turic Csokova [verfasserIn] Karina Markova [verfasserIn] Michaela Skrabanova [verfasserIn] Kristina Sinska [verfasserIn] Neha Basheer [verfasserIn] Petra Majerova [verfasserIn] Jozef Hanes [verfasserIn] Vojtech Parrak [verfasserIn] Michal Prcina [verfasserIn] Ondrej Cehlar [verfasserIn] Martin Cente [verfasserIn] Juraj Piestansky [verfasserIn] Michal Fresser [verfasserIn] Michal Novak [verfasserIn] Monika Slavikova [verfasserIn] Kristina Borsova [verfasserIn] Viktoria Cabanova [verfasserIn] Bronislava Brejova [verfasserIn] Tomas Vinař [verfasserIn] Jozef Nosek [verfasserIn] Boris Klempa [verfasserIn] Ludek Eyer [verfasserIn] Vaclav Hönig [verfasserIn] Martin Palus [verfasserIn] Daniel Ruzek [verfasserIn] Tereza Vyhlidalova [verfasserIn] Petra Strakova [verfasserIn] Blanka Mrazkova [verfasserIn] Dagmar Zudova [verfasserIn] Gizela Koubkova [verfasserIn] Vendula Novosadova [verfasserIn] Jan Prochazka [verfasserIn] Radislav Sedlacek [verfasserIn] Norbert Zilka [verfasserIn] Eva Kontsekova [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: EBioMedicine - Elsevier, 2015, 76(2022), Seite 103818- |
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| Übergeordnetes Werk: |
volume:76 ; year:2022 ; pages:103818- |
| Links: |
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| DOI / URN: |
10.1016/j.ebiom.2022.103818 |
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| Katalog-ID: |
DOAJ086599356 |
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| 100 | 0 | |a Branislav Kovacech |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern |
| 264 | 1 | |c 2022 | |
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| 520 | |a Summary: 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. | ||
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Neutralizing antibodies | |
| 650 | 4 | |a Escape mutation | |
| 650 | 4 | |a Variants of concern | |
| 653 | 0 | |a Medicine | |
| 653 | 0 | |a R | |
| 653 | 0 | |a Medicine (General) | |
| 700 | 0 | |a Lubica Fialova |e verfasserin |4 aut | |
| 700 | 0 | |a Peter Filipcik |e verfasserin |4 aut | |
| 700 | 0 | |a Rostislav Skrabana |e verfasserin |4 aut | |
| 700 | 0 | |a Monika Zilkova |e verfasserin |4 aut | |
| 700 | 0 | |a Natalia Paulenka-Ivanovova |e verfasserin |4 aut | |
| 700 | 0 | |a Andrej Kovac |e verfasserin |4 aut | |
| 700 | 0 | |a Denisa Palova |e verfasserin |4 aut | |
| 700 | 0 | |a Gabriela Paulikova Rolkova |e verfasserin |4 aut | |
| 700 | 0 | |a Katarina Tomkova |e verfasserin |4 aut | |
| 700 | 0 | |a Natalia Turic Csokova |e verfasserin |4 aut | |
| 700 | 0 | |a Karina Markova |e verfasserin |4 aut | |
| 700 | 0 | |a Michaela Skrabanova |e verfasserin |4 aut | |
| 700 | 0 | |a Kristina Sinska |e verfasserin |4 aut | |
| 700 | 0 | |a Neha Basheer |e verfasserin |4 aut | |
| 700 | 0 | |a Petra Majerova |e verfasserin |4 aut | |
| 700 | 0 | |a Jozef Hanes |e verfasserin |4 aut | |
| 700 | 0 | |a Vojtech Parrak |e verfasserin |4 aut | |
| 700 | 0 | |a Michal Prcina |e verfasserin |4 aut | |
| 700 | 0 | |a Ondrej Cehlar |e verfasserin |4 aut | |
| 700 | 0 | |a Martin Cente |e verfasserin |4 aut | |
| 700 | 0 | |a Juraj Piestansky |e verfasserin |4 aut | |
| 700 | 0 | |a Michal Fresser |e verfasserin |4 aut | |
| 700 | 0 | |a Michal Novak |e verfasserin |4 aut | |
| 700 | 0 | |a Monika Slavikova |e verfasserin |4 aut | |
| 700 | 0 | |a Kristina Borsova |e verfasserin |4 aut | |
| 700 | 0 | |a Viktoria Cabanova |e verfasserin |4 aut | |
| 700 | 0 | |a Bronislava Brejova |e verfasserin |4 aut | |
| 700 | 0 | |a Tomas Vinař |e verfasserin |4 aut | |
| 700 | 0 | |a Jozef Nosek |e verfasserin |4 aut | |
| 700 | 0 | |a Boris Klempa |e verfasserin |4 aut | |
| 700 | 0 | |a Ludek Eyer |e verfasserin |4 aut | |
| 700 | 0 | |a Vaclav Hönig |e verfasserin |4 aut | |
| 700 | 0 | |a Martin Palus |e verfasserin |4 aut | |
| 700 | 0 | |a Daniel Ruzek |e verfasserin |4 aut | |
| 700 | 0 | |a Tereza Vyhlidalova |e verfasserin |4 aut | |
| 700 | 0 | |a Petra Strakova |e verfasserin |4 aut | |
| 700 | 0 | |a Blanka Mrazkova |e verfasserin |4 aut | |
| 700 | 0 | |a Dagmar Zudova |e verfasserin |4 aut | |
| 700 | 0 | |a Gizela Koubkova |e verfasserin |4 aut | |
| 700 | 0 | |a Vendula Novosadova |e verfasserin |4 aut | |
| 700 | 0 | |a Jan Prochazka |e verfasserin |4 aut | |
| 700 | 0 | |a Radislav Sedlacek |e verfasserin |4 aut | |
| 700 | 0 | |a Norbert Zilka |e verfasserin |4 aut | |
| 700 | 0 | |a Eva Kontsekova |e verfasserin |4 aut | |
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10.1016/j.ebiom.2022.103818 doi (DE-627)DOAJ086599356 (DE-599)DOAJd503988bb92a4f8ca2f39b041da95550 DE-627 ger DE-627 rakwb eng R5-920 Branislav Kovacech verfasserin aut Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. SARS-CoV-2 COVID-19 Neutralizing antibodies Escape mutation Variants of concern Medicine R Medicine (General) Lubica Fialova verfasserin aut Peter Filipcik verfasserin aut Rostislav Skrabana verfasserin aut Monika Zilkova verfasserin aut Natalia Paulenka-Ivanovova verfasserin aut Andrej Kovac verfasserin aut Denisa Palova verfasserin aut Gabriela Paulikova Rolkova verfasserin aut Katarina Tomkova verfasserin aut Natalia Turic Csokova verfasserin aut Karina Markova verfasserin aut Michaela Skrabanova verfasserin aut Kristina Sinska verfasserin aut Neha Basheer verfasserin aut Petra Majerova verfasserin aut Jozef Hanes verfasserin aut Vojtech Parrak verfasserin aut Michal Prcina verfasserin aut Ondrej Cehlar verfasserin aut Martin Cente verfasserin aut Juraj Piestansky verfasserin aut Michal Fresser verfasserin aut Michal Novak verfasserin aut Monika Slavikova verfasserin aut Kristina Borsova verfasserin aut Viktoria Cabanova verfasserin aut Bronislava Brejova verfasserin aut Tomas Vinař verfasserin aut Jozef Nosek verfasserin aut Boris Klempa verfasserin aut Ludek Eyer verfasserin aut Vaclav Hönig verfasserin aut Martin Palus verfasserin aut Daniel Ruzek verfasserin aut Tereza Vyhlidalova verfasserin aut Petra Strakova verfasserin aut Blanka Mrazkova verfasserin aut Dagmar Zudova verfasserin aut Gizela Koubkova verfasserin aut Vendula Novosadova verfasserin aut Jan Prochazka verfasserin aut Radislav Sedlacek verfasserin aut Norbert Zilka verfasserin aut Eva Kontsekova verfasserin aut In EBioMedicine Elsevier, 2015 76(2022), Seite 103818- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:76 year:2022 pages:103818- https://doi.org/10.1016/j.ebiom.2022.103818 kostenfrei https://doaj.org/article/d503988bb92a4f8ca2f39b041da95550 kostenfrei http://www.sciencedirect.com/science/article/pii/S235239642200007X kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 76 2022 103818- |
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10.1016/j.ebiom.2022.103818 doi (DE-627)DOAJ086599356 (DE-599)DOAJd503988bb92a4f8ca2f39b041da95550 DE-627 ger DE-627 rakwb eng R5-920 Branislav Kovacech verfasserin aut Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. SARS-CoV-2 COVID-19 Neutralizing antibodies Escape mutation Variants of concern Medicine R Medicine (General) Lubica Fialova verfasserin aut Peter Filipcik verfasserin aut Rostislav Skrabana verfasserin aut Monika Zilkova verfasserin aut Natalia Paulenka-Ivanovova verfasserin aut Andrej Kovac verfasserin aut Denisa Palova verfasserin aut Gabriela Paulikova Rolkova verfasserin aut Katarina Tomkova verfasserin aut Natalia Turic Csokova verfasserin aut Karina Markova verfasserin aut Michaela Skrabanova verfasserin aut Kristina Sinska verfasserin aut Neha Basheer verfasserin aut Petra Majerova verfasserin aut Jozef Hanes verfasserin aut Vojtech Parrak verfasserin aut Michal Prcina verfasserin aut Ondrej Cehlar verfasserin aut Martin Cente verfasserin aut Juraj Piestansky verfasserin aut Michal Fresser verfasserin aut Michal Novak verfasserin aut Monika Slavikova verfasserin aut Kristina Borsova verfasserin aut Viktoria Cabanova verfasserin aut Bronislava Brejova verfasserin aut Tomas Vinař verfasserin aut Jozef Nosek verfasserin aut Boris Klempa verfasserin aut Ludek Eyer verfasserin aut Vaclav Hönig verfasserin aut Martin Palus verfasserin aut Daniel Ruzek verfasserin aut Tereza Vyhlidalova verfasserin aut Petra Strakova verfasserin aut Blanka Mrazkova verfasserin aut Dagmar Zudova verfasserin aut Gizela Koubkova verfasserin aut Vendula Novosadova verfasserin aut Jan Prochazka verfasserin aut Radislav Sedlacek verfasserin aut Norbert Zilka verfasserin aut Eva Kontsekova verfasserin aut In EBioMedicine Elsevier, 2015 76(2022), Seite 103818- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:76 year:2022 pages:103818- https://doi.org/10.1016/j.ebiom.2022.103818 kostenfrei https://doaj.org/article/d503988bb92a4f8ca2f39b041da95550 kostenfrei http://www.sciencedirect.com/science/article/pii/S235239642200007X kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 76 2022 103818- |
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10.1016/j.ebiom.2022.103818 doi (DE-627)DOAJ086599356 (DE-599)DOAJd503988bb92a4f8ca2f39b041da95550 DE-627 ger DE-627 rakwb eng R5-920 Branislav Kovacech verfasserin aut Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. SARS-CoV-2 COVID-19 Neutralizing antibodies Escape mutation Variants of concern Medicine R Medicine (General) Lubica Fialova verfasserin aut Peter Filipcik verfasserin aut Rostislav Skrabana verfasserin aut Monika Zilkova verfasserin aut Natalia Paulenka-Ivanovova verfasserin aut Andrej Kovac verfasserin aut Denisa Palova verfasserin aut Gabriela Paulikova Rolkova verfasserin aut Katarina Tomkova verfasserin aut Natalia Turic Csokova verfasserin aut Karina Markova verfasserin aut Michaela Skrabanova verfasserin aut Kristina Sinska verfasserin aut Neha Basheer verfasserin aut Petra Majerova verfasserin aut Jozef Hanes verfasserin aut Vojtech Parrak verfasserin aut Michal Prcina verfasserin aut Ondrej Cehlar verfasserin aut Martin Cente verfasserin aut Juraj Piestansky verfasserin aut Michal Fresser verfasserin aut Michal Novak verfasserin aut Monika Slavikova verfasserin aut Kristina Borsova verfasserin aut Viktoria Cabanova verfasserin aut Bronislava Brejova verfasserin aut Tomas Vinař verfasserin aut Jozef Nosek verfasserin aut Boris Klempa verfasserin aut Ludek Eyer verfasserin aut Vaclav Hönig verfasserin aut Martin Palus verfasserin aut Daniel Ruzek verfasserin aut Tereza Vyhlidalova verfasserin aut Petra Strakova verfasserin aut Blanka Mrazkova verfasserin aut Dagmar Zudova verfasserin aut Gizela Koubkova verfasserin aut Vendula Novosadova verfasserin aut Jan Prochazka verfasserin aut Radislav Sedlacek verfasserin aut Norbert Zilka verfasserin aut Eva Kontsekova verfasserin aut In EBioMedicine Elsevier, 2015 76(2022), Seite 103818- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:76 year:2022 pages:103818- https://doi.org/10.1016/j.ebiom.2022.103818 kostenfrei https://doaj.org/article/d503988bb92a4f8ca2f39b041da95550 kostenfrei http://www.sciencedirect.com/science/article/pii/S235239642200007X kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 76 2022 103818- |
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10.1016/j.ebiom.2022.103818 doi (DE-627)DOAJ086599356 (DE-599)DOAJd503988bb92a4f8ca2f39b041da95550 DE-627 ger DE-627 rakwb eng R5-920 Branislav Kovacech verfasserin aut Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. SARS-CoV-2 COVID-19 Neutralizing antibodies Escape mutation Variants of concern Medicine R Medicine (General) Lubica Fialova verfasserin aut Peter Filipcik verfasserin aut Rostislav Skrabana verfasserin aut Monika Zilkova verfasserin aut Natalia Paulenka-Ivanovova verfasserin aut Andrej Kovac verfasserin aut Denisa Palova verfasserin aut Gabriela Paulikova Rolkova verfasserin aut Katarina Tomkova verfasserin aut Natalia Turic Csokova verfasserin aut Karina Markova verfasserin aut Michaela Skrabanova verfasserin aut Kristina Sinska verfasserin aut Neha Basheer verfasserin aut Petra Majerova verfasserin aut Jozef Hanes verfasserin aut Vojtech Parrak verfasserin aut Michal Prcina verfasserin aut Ondrej Cehlar verfasserin aut Martin Cente verfasserin aut Juraj Piestansky verfasserin aut Michal Fresser verfasserin aut Michal Novak verfasserin aut Monika Slavikova verfasserin aut Kristina Borsova verfasserin aut Viktoria Cabanova verfasserin aut Bronislava Brejova verfasserin aut Tomas Vinař verfasserin aut Jozef Nosek verfasserin aut Boris Klempa verfasserin aut Ludek Eyer verfasserin aut Vaclav Hönig verfasserin aut Martin Palus verfasserin aut Daniel Ruzek verfasserin aut Tereza Vyhlidalova verfasserin aut Petra Strakova verfasserin aut Blanka Mrazkova verfasserin aut Dagmar Zudova verfasserin aut Gizela Koubkova verfasserin aut Vendula Novosadova verfasserin aut Jan Prochazka verfasserin aut Radislav Sedlacek verfasserin aut Norbert Zilka verfasserin aut Eva Kontsekova verfasserin aut In EBioMedicine Elsevier, 2015 76(2022), Seite 103818- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:76 year:2022 pages:103818- https://doi.org/10.1016/j.ebiom.2022.103818 kostenfrei https://doaj.org/article/d503988bb92a4f8ca2f39b041da95550 kostenfrei http://www.sciencedirect.com/science/article/pii/S235239642200007X kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 76 2022 103818- |
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10.1016/j.ebiom.2022.103818 doi (DE-627)DOAJ086599356 (DE-599)DOAJd503988bb92a4f8ca2f39b041da95550 DE-627 ger DE-627 rakwb eng R5-920 Branislav Kovacech verfasserin aut Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. SARS-CoV-2 COVID-19 Neutralizing antibodies Escape mutation Variants of concern Medicine R Medicine (General) Lubica Fialova verfasserin aut Peter Filipcik verfasserin aut Rostislav Skrabana verfasserin aut Monika Zilkova verfasserin aut Natalia Paulenka-Ivanovova verfasserin aut Andrej Kovac verfasserin aut Denisa Palova verfasserin aut Gabriela Paulikova Rolkova verfasserin aut Katarina Tomkova verfasserin aut Natalia Turic Csokova verfasserin aut Karina Markova verfasserin aut Michaela Skrabanova verfasserin aut Kristina Sinska verfasserin aut Neha Basheer verfasserin aut Petra Majerova verfasserin aut Jozef Hanes verfasserin aut Vojtech Parrak verfasserin aut Michal Prcina verfasserin aut Ondrej Cehlar verfasserin aut Martin Cente verfasserin aut Juraj Piestansky verfasserin aut Michal Fresser verfasserin aut Michal Novak verfasserin aut Monika Slavikova verfasserin aut Kristina Borsova verfasserin aut Viktoria Cabanova verfasserin aut Bronislava Brejova verfasserin aut Tomas Vinař verfasserin aut Jozef Nosek verfasserin aut Boris Klempa verfasserin aut Ludek Eyer verfasserin aut Vaclav Hönig verfasserin aut Martin Palus verfasserin aut Daniel Ruzek verfasserin aut Tereza Vyhlidalova verfasserin aut Petra Strakova verfasserin aut Blanka Mrazkova verfasserin aut Dagmar Zudova verfasserin aut Gizela Koubkova verfasserin aut Vendula Novosadova verfasserin aut Jan Prochazka verfasserin aut Radislav Sedlacek verfasserin aut Norbert Zilka verfasserin aut Eva Kontsekova verfasserin aut In EBioMedicine Elsevier, 2015 76(2022), Seite 103818- (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:76 year:2022 pages:103818- https://doi.org/10.1016/j.ebiom.2022.103818 kostenfrei https://doaj.org/article/d503988bb92a4f8ca2f39b041da95550 kostenfrei http://www.sciencedirect.com/science/article/pii/S235239642200007X kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 76 2022 103818- |
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Branislav Kovacech @@aut@@ Lubica Fialova @@aut@@ Peter Filipcik @@aut@@ Rostislav Skrabana @@aut@@ Monika Zilkova @@aut@@ Natalia Paulenka-Ivanovova @@aut@@ Andrej Kovac @@aut@@ Denisa Palova @@aut@@ Gabriela Paulikova Rolkova @@aut@@ Katarina Tomkova @@aut@@ Natalia Turic Csokova @@aut@@ Karina Markova @@aut@@ Michaela Skrabanova @@aut@@ Kristina Sinska @@aut@@ Neha Basheer @@aut@@ Petra Majerova @@aut@@ Jozef Hanes @@aut@@ Vojtech Parrak @@aut@@ Michal Prcina @@aut@@ Ondrej Cehlar @@aut@@ Martin Cente @@aut@@ Juraj Piestansky @@aut@@ Michal Fresser @@aut@@ Michal Novak @@aut@@ Monika Slavikova @@aut@@ Kristina Borsova @@aut@@ Viktoria Cabanova @@aut@@ Bronislava Brejova @@aut@@ Tomas Vinař @@aut@@ Jozef Nosek @@aut@@ Boris Klempa @@aut@@ Ludek Eyer @@aut@@ Vaclav Hönig @@aut@@ Martin Palus @@aut@@ Daniel Ruzek @@aut@@ Tereza Vyhlidalova @@aut@@ Petra Strakova @@aut@@ Blanka Mrazkova @@aut@@ Dagmar Zudova @@aut@@ Gizela Koubkova @@aut@@ Vendula Novosadova @@aut@@ Jan Prochazka @@aut@@ Radislav Sedlacek @@aut@@ Norbert Zilka @@aut@@ Eva Kontsekova @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ086599356</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230311052058.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230311s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ebiom.2022.103818</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ086599356</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJd503988bb92a4f8ca2f39b041da95550</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">R5-920</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Branislav Kovacech</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Summary: 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. 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|
| callnumber-first |
R - Medicine |
| author |
Branislav Kovacech |
| spellingShingle |
Branislav Kovacech misc R5-920 misc SARS-CoV-2 misc COVID-19 misc Neutralizing antibodies misc Escape mutation misc Variants of concern misc Medicine misc R misc Medicine (General) Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern |
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Branislav Kovacech |
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electronic Article |
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keep |
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true |
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R5-920 |
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Not Illustrated |
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23523964 |
| topic_title |
R5-920 Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern SARS-CoV-2 COVID-19 Neutralizing antibodies Escape mutation Variants of concern |
| topic |
misc R5-920 misc SARS-CoV-2 misc COVID-19 misc Neutralizing antibodies misc Escape mutation misc Variants of concern misc Medicine misc R misc Medicine (General) |
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Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern |
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Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern |
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Branislav Kovacech |
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103818 |
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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 Vinař Jozef Nosek Boris Klempa Ludek Eyer Vaclav Hönig Martin Palus Daniel Ruzek Tereza Vyhlidalova Petra Strakova Blanka Mrazkova Dagmar Zudova Gizela Koubkova Vendula Novosadova Jan Prochazka Radislav Sedlacek Norbert Zilka Eva Kontsekova |
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Branislav Kovacech |
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10.1016/j.ebiom.2022.103818 |
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monoclonal antibodies targeting two immunodominant epitopes on the spike protein neutralize emerging sars-cov-2 variants of concern |
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R5-920 |
| title_auth |
Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern |
| abstract |
Summary: 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. |
| abstractGer |
Summary: 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. |
| abstract_unstemmed |
Summary: 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. |
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Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern |
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https://doi.org/10.1016/j.ebiom.2022.103818 https://doaj.org/article/d503988bb92a4f8ca2f39b041da95550 http://www.sciencedirect.com/science/article/pii/S235239642200007X https://doaj.org/toc/2352-3964 |
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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 Ludek Eyer Vaclav Hönig Martin Palus Daniel Ruzek Tereza Vyhlidalova Petra Strakova Blanka Mrazkova Dagmar Zudova Gizela Koubkova Vendula Novosadova Jan Prochazka Radislav Sedlacek Norbert Zilka Eva Kontsekova |
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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 Ludek Eyer Vaclav Hönig Martin Palus Daniel Ruzek Tereza Vyhlidalova Petra Strakova Blanka Mrazkova Dagmar Zudova Gizela Koubkova Vendula Novosadova Jan Prochazka Radislav Sedlacek Norbert Zilka Eva Kontsekova |
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