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Development of Safe and Highly Protective Live-Attenuated SARS-CoV-2 Vaccine Candidates by Genome Recoding

43 Pages Posted: 10 Feb 2021 Publication Status: Published

See all articles by Jakob Trimpert

Jakob Trimpert

Free University of Berlin (FUB) - Institut für Virologie

Kristina Dietert

Free University of Berlin (FUB) - Institut für Tierpathologie

Nadine Ebert

University of Bern - Institute of Virology and Immunology

Tran Thi Nhu Thao

University of Bern - Institute of Virology and Immunology

Daria Vladimirova

Free University of Berlin (FUB) - Institut für Virologie

Susanne Kaufer

Free University of Berlin (FUB) - Institut für Virologie

Fabien Labroussaa

University of Bern - Department of Infectious Diseases and Pathobiology

Azza Abdelgawad

Free University of Berlin (FUB) - Institut für Virologie

Andelé Conradie

Free University of Berlin (FUB) - Institut für Virologie

Thomas Höfler

Free University of Berlin (FUB) - Institut für Virologie

Julia M. Adler

Free University of Berlin (FUB) - Institut für Virologie

Luca Bertzbach

Free University of Berlin (FUB) - Institut für Virologie

Joerg Jores

University of Bern - Department of Infectious Diseases and Pathobiology

Achim Gruber

Free University of Berlin (FUB) - Institut für Tierpathologie

Volker Thiel

University of Bern - Institute of Virology and Immunology

Nikolaus Osterrieder

Free University of Berlin (FUB) - Institut für Virologie

Dusan Kunec

Free University of Berlin (FUB) - Institut für Virologie

More...

Abstract

Safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We constructed a series of live attenuated vaccine candidates by large-scale recoding of the SARS-CoV-2 genome, and assessed their safety and efficacy in Syrian hamsters. Animals were vaccinated with a single dose of the respective recoded virus and challenged 21 days later. Two of the tested viruses did not cause clinical symptoms, but were highly immunogenic and induced strong protective immunity. Attenuated viruses replicated efficiently in the upper but not in the lower airways, causing only mild pulmonary histopathology. After challenge, hamsters developed no signs of disease and rapidly cleared challenge virus: at no time could infectious virus be recovered from the lungs of infected animals. The ease with which attenuated virus candidates can be produced and administered favors their further development as vaccines to combat the ongoing pandemic.

Funding: This research was supported by the Deutsche Forschungsgemeinschaft (DFG), grant OS143/16-1 and COVID-19 grants from Freie Universität Berlin and Berlin University Alliance awarded to NO, the DFG grant SFB-TR84/Z01b awarded to ADG and JT and the SwissNational Science Foundation, grants 31CA30_196644, 31CA30_196062, and 310030_173085 awarded to VT.

Conflict of Interest: The authors declare no competing interests.

Ethical Approval: In vitro and animal work was done under biosafety conditions in the BSL-3 facility at the Institut für Virologie, Freie Universität Berlin, Germany. All animal experiments wereapproved by the Landesamt für Gesundheit und Soziales in Berlin, Germany (permit number0086/20) and done in compliance with relevant national and international guidelines for care and humane use of animals.

Keywords: coronavirus, SARS-CoV-2, COVID-19, live attenuated vaccine, genome recoding, codon pair deoptimization, synthetic attenuated virus engineering, Syrian hamster

Suggested Citation

Trimpert, Jakob and Dietert, Kristina and Ebert, Nadine and Thao, Tran Thi Nhu and Vladimirova, Daria and Kaufer, Susanne and Labroussaa, Fabien and Abdelgawad, Azza and Conradie, Andelé and Höfler, Thomas and Adler, Julia M. and Bertzbach, Luca and Jores, Joerg and Gruber, Achim and Thiel, Volker and Osterrieder, Nikolaus and Kunec, Dusan, Development of Safe and Highly Protective Live-Attenuated SARS-CoV-2 Vaccine Candidates by Genome Recoding. Available at SSRN: https://ssrn.com/abstract=3783405 or http://dx.doi.org/10.2139/ssrn.3783405
This version of the paper has not been formally peer reviewed.

Jakob Trimpert

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Kristina Dietert

Free University of Berlin (FUB) - Institut für Tierpathologie ( email )

Van't-Hoff-Str. 8
Berlin, Berlin 14195
Germany

Nadine Ebert

University of Bern - Institute of Virology and Immunology ( email )

Gesellschaftsstrasse 49
Bern, BERN 3001
Switzerland

Tran Thi Nhu Thao

University of Bern - Institute of Virology and Immunology ( email )

Gesellschaftsstrasse 49
Bern, BERN 3001
Switzerland

Daria Vladimirova

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Susanne Kaufer

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Fabien Labroussaa

University of Bern - Department of Infectious Diseases and Pathobiology ( email )

Gesellschaftsstrasse 49
Bern, BERN 3001
Switzerland

Azza Abdelgawad

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Andelé Conradie

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Thomas Höfler

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Julia M. Adler

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Luca Bertzbach

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Joerg Jores

University of Bern - Department of Infectious Diseases and Pathobiology ( email )

Gesellschaftsstrasse 49
Bern, BERN 3001
Switzerland

Achim Gruber

Free University of Berlin (FUB) - Institut für Tierpathologie ( email )

Van't-Hoff-Str. 8
Berlin, Berlin 14195
Germany

Volker Thiel

University of Bern - Institute of Virology and Immunology ( email )

Gesellschaftsstrasse 49
Bern, BERN 3001
Switzerland

Nikolaus Osterrieder

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Dusan Kunec (Contact Author)

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

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