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Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease
Raoul De Gasparo; Mattia Pedotti; Luca Simonelli; Petr Nickl; Frauke Muecksch; Irene Cassaniti; Elena Percivalle; Julio C. C. Lorenzi; Federica Mazzola; Davide Magrì; Tereza Michalcikova; Jan Haviernik; Vaclav Honig; Blanka Mrazkova; Natalie Polakova; Andrea Fortova; Jolana Tureckova; Veronika Iatsiuk; Salvatore Di Girolamo; Martin Palus; Dagmar Zudova; Petr Bednar; Ivana Bukova; Filippo Bianchini; Dora Mehn; Radim Nencka; Petra Strakova; Oto Pavlis; Jan Rozman; Sabrina Gioria; Josè Camilla Sammartino; Federica Giardina; Stefano Gaiarsa; Qiang Pan Hammarström; Christopher O. Barnes; Pamela J. Bjorkman; Luigi Calzolai; Antonio Piralla; Fausto Baldanti; Michel C. Nussenzweig; Paul D. Bieniasz; Theodora Hatziioannou; Jan Prochazka; Radislav Sedlacek; Davide F. Robbiani; Daniel Ruzek; Luca Varani.
Afiliação
  • Raoul De Gasparo; Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
  • Mattia Pedotti; Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
  • Luca Simonelli; Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
  • Petr Nickl; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Frauke Muecksch; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA
  • Irene Cassaniti; Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Elena Percivalle; Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Julio C. C. Lorenzi; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA
  • Federica Mazzola; Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
  • Davide Magrì; European Commission, Joint Research Centre, Ispra, VA, Italy
  • Tereza Michalcikova; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Jan Haviernik; Veterinary Research Institute, Brno, Czech Republic
  • Vaclav Honig; Veterinary Research Institute, Brno, Czech Republic and Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Repu
  • Blanka Mrazkova; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Natalie Polakova; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Andrea Fortova; Veterinary Research Institute, Brno, Czech Republic
  • Jolana Tureckova; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Veronika Iatsiuk; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Salvatore Di Girolamo; Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
  • Martin Palus; Veterinary Research Institute, Brno, Czech Republic and Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Repu
  • Dagmar Zudova; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Petr Bednar; Veterinary Research Institute, Brno, Czech Republic and Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic
  • Ivana Bukova; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Filippo Bianchini; Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
  • Dora Mehn; European Commission, Joint Research Centre, Ispra, VA, Italy
  • Radim Nencka; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic
  • Petra Strakova; Veterinary Research Institute, Brno, Czech Republic
  • Oto Pavlis; Center of Biological Defense, Military Health Institute, Military Medical Agency, Techonin, Czech Republic
  • Jan Rozman; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Sabrina Gioria; European Commission, Joint Research Centre, Ispra, VA, Italy
  • Josè Camilla Sammartino; Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Federica Giardina; Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Stefano Gaiarsa; Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Qiang Pan Hammarström; Department of Biosciences and Nutrition, Karolinska Institutet, SE14183, Huddinge, Sweden
  • Christopher O. Barnes; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Pamela J. Bjorkman; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Luigi Calzolai; European Commission, Joint Research Centre, Ispra, VA, Italy
  • Antonio Piralla; Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Fausto Baldanti; Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Michel C. Nussenzweig; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA and Howard Hughes Medical Institute, The Rockefeller University, New York, NY,
  • Paul D. Bieniasz; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA and Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA
  • Theodora Hatziioannou; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA
  • Jan Prochazka; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Radislav Sedlacek; Czech Centre of Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
  • Davide F. Robbiani; Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
  • Daniel Ruzek; Veterinary Research Institute, Brno, Czech Republic and Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Repu
  • Luca Varani; Institute for Research in Biomedicine, Università della Svizzera Italiana
Preprint em En | PREPRINT-BIORXIV | ID: ppbiorxiv-427567
ABSTRACT
Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)1,2. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C1353. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint