SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface
SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface
Abstract COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a novel betacoronavirus discovered in December 2019 and closely related to the SARS coronavirus (CoV). Both viruses use the human ACE2 receptor for cell entry, recognizing it with the Receptor Binding Domain (RBD) of the S1 subunit of the viral spike (S) protein. The S2 domain mediates viral fusion with the host cell membrane. Experience with SARS and MERS coronaviruses has shown that potent monoclonal neutralizing antibodies against the RBD can inhibit the interaction with the virus cellular receptor (ACE2 for SARS) and block the virus cell entry. Assuming that a similar strategy would be successful against SARS-CoV-2, we used phage display to select from the human na?ve universal antibody gene libraries HAL9/10 anti-SARS-CoV-2 spike antibodies capable of inhibiting interaction with ACE2. 309 unique fully human antibodies against S1 were identified. 17 showed more than 75% inhibition of spike binding to cells expressing ACE2 in the scFv-Fc format, assessed by flow cytometry and several antibodies showed even an 50% inhibition at a molar ratio of the antibody to spike protein or RBD of 1:1. All 17 scFv-Fc were able to bind the isolated RBD, four of them with sub-nanomolar EC50. Furthermore, these scFv-Fc neutralized active SARS-CoV-2 virus infection of VeroE6 cells. In a final step, the antibodies neutralizing best as scFv-Fc were converted into the IgG format. The antibody STE73-2E9 showed neutralization of active SARS-CoV-2 with an IC50 0.43 nM and is binding to the ACE2-RBD interface. Universal libraries from healthy human donors offer the advantage that antibodies can be generated quickly and independent from the availability of material from recovered patients in a pandemic situation.
Bertoglio Federico、Varani Luca、Steinke Stephan、Brunotte Linda、F¨1hner Viola、D¨1bel Stefan、Schubert Maren、Kuhn Philipp、W?hrle Johannes、Kilb Normann、Wenzel Esther Veronika、Riese Peggy、Eschke Kathrin、Kim Yeonsu、Ballmann Rico、Ruschig Maximilian、Heine Philip Alexander、Simonelli Luca、?i?in-?ain Luka、Sch?ckermann Dorina、Meier Doris、Zock-Emmenthal Susanne、Hust Michael、Grasshoff Martina、Schneider Kai-Thomas、Kr?ger Andrea、Herz Tobias、Becker Marlies、Langreder Nora、Kr?mer Stefan Daniel、Pedotti Mattia、Roth Kristian Daniel Ralph、Russo Giulio、Ludwig Stephan、Rand Ulfert、Roth G¨1nter
Technische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieIstituto di Ricerca in Biomedicina (IRB), Universita?ˉ della Svizzera italianaTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieWestf?lische Wilhelms-Universit?t M¨1nster, Institut f¨1r Virologie (IVM)Technische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieYUMAB GmbH, Inhoffenstr. 7BioCopy GmbHBioCopy GmbHTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie||Helmholtz Centre for Infection Research, Department of Vaccinology and Applied MicrobiologyHelmholtz Centre for Infection Research, Department of Vaccinology and Applied MicrobiologyHelmholtz Centre for Infection Research, Department of Vaccinology and Applied MicrobiologyTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieIstituto di Ricerca in Biomedicina (IRB), Universita?ˉ della Svizzera italianaHelmholtz Centre for Infection Research, Department of Vaccinology and Applied Microbiology||Centre for Individualised Infection Medicine (CIIM), a joint venture of Helmholtz Centre for Infection Research and Medical School HannoverTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r GenetikTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieHelmholtz Centre for Infection Research, Research Group Innate Immunity and InfectionTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieHelmholtz Centre for Infection Research, Research Group Innate Immunity and InfectionBioCopy GmbHTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieBioCopy GmbHIstituto di Ricerca in Biomedicina (IRB), Universita?ˉ della Svizzera italianaTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieTechnische Universit?t Braunschweig, Institut f¨1r Biochemie, Biotechnologie und Bioinformatik, Abteilung BiotechnologieWestf?lische Wilhelms-Universit?t M¨1nster, Institut f¨1r Virologie (IVM)Helmholtz Centre for Infection Research, Department of Vaccinology and Applied MicrobiologyBioCopy GmbH
医学研究方法基础医学生物科学研究方法、生物科学研究技术
Bertoglio Federico,Varani Luca,Steinke Stephan,Brunotte Linda,F¨1hner Viola,D¨1bel Stefan,Schubert Maren,Kuhn Philipp,W?hrle Johannes,Kilb Normann,Wenzel Esther Veronika,Riese Peggy,Eschke Kathrin,Kim Yeonsu,Ballmann Rico,Ruschig Maximilian,Heine Philip Alexander,Simonelli Luca,?i?in-?ain Luka,Sch?ckermann Dorina,Meier Doris,Zock-Emmenthal Susanne,Hust Michael,Grasshoff Martina,Schneider Kai-Thomas,Kr?ger Andrea,Herz Tobias,Becker Marlies,Langreder Nora,Kr?mer Stefan Daniel,Pedotti Mattia,Roth Kristian Daniel Ralph,Russo Giulio,Ludwig Stephan,Rand Ulfert,Roth G¨1nter.SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2020.06.05.135921.点此复制
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