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Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination
Alina Tscherne; Jan Hendrik Schwarz; Cornelius Rohde; Alexandra Kupke; Georgia Kalodimou; Leonard Limpinsel; Nisreen M.A. Okba; Berislav Bosnjak; Inga Sandrock; Sandro Halwe; Lucie Sauerhering; Katrin Printz; Liangliang Nan; Elke Duell; Sylvia Jany; Astrid Freudenstein; Joerg Schmidt; Anke Werner; Michelle Gellhorn; Michael Kluever; Wolfgang Guggemos; Michael Seilmaier; Clemens Wendtner; Reinhold Foerster; Bart Haagmans; Stephan Becker; Gerd Sutter; Asisa Volz.
Affiliation
  • Alina Tscherne; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Jan Hendrik Schwarz; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Cornelius Rohde; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Alexandra Kupke; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Georgia Kalodimou; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Leonard Limpinsel; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Nisreen M.A. Okba; Erasmus MC
  • Berislav Bosnjak; Institute of Immunology, Hannover Medical School, Hannover, Germany
  • Inga Sandrock; Institute of Immunology, Hannover Medical School, Hannover, Germany
  • Sandro Halwe; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Lucie Sauerhering; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Katrin Printz; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Liangliang Nan; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Elke Duell; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Sylvia Jany; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Astrid Freudenstein; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Joerg Schmidt; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Anke Werner; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Michelle Gellhorn; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Michael Kluever; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Wolfgang Guggemos; Munich Clinic Schwabing, Academic Teaching Hospital, LMU Munich, Munich, Germany
  • Michael Seilmaier; Munich Clinic Schwabing, Academic Teaching Hospital, LMU Munich, Munich, Germany
  • Clemens Wendtner; Munich Clinic Schwabing, Academic Teaching Hospital, LMU Munich, Munich, Germany
  • Reinhold Foerster; Institute of Immunology, Hannover Medical School, Hannover, Germany
  • Bart Haagmans; Erasmus Medical Center
  • Stephan Becker; Institute of Virology, Philipps University Marburg, Marburg, Germany
  • Gerd Sutter; Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany
  • Asisa Volz; University of Veterinary Medicine Hannover
Preprint in English | bioRxiv | ID: ppbiorxiv-426032
ABSTRACT
The severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on vaccinia virus MVA against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust synthesis of S antigen, make it a suitable candidate vaccine for industrial scale production. Vaccinated mice produced S antigen-specific CD8+ T cells and serum antibodies binding to S glycoprotein that neutralized SARS-CoV-2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19. Significance StatementThe highly attenuated vaccinia virus MVA is licensed as smallpox vaccine, and as vector it is a component of the approved Adenovirus-MVA-based prime-boost vaccine against Ebola virus disease. Here we provide results from testing the COVID-19 candidate vaccine MVA-SARS-2-S, a poxvirus-based vector vaccine that proceeded to clinical evaluation. When administered by intramuscular inoculation, MVA-SARS-2-S expresses and safely delivers the full-length SARS-CoV-2 spike (S) protein, inducing balanced SARS-CoV-2-specific cellular and humoral immunity, and protective efficacy in vaccinated mice. Substantial clinical experience has already been gained with MVA vectors using homologous and heterologous prime-boost applications, including the immunization of children and immunocompromised individuals. Thus, MVA-SARS-2-S represents an important resource for developing further optimized COVID-19 vaccines.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study / Rct Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study / Rct Language: English Year: 2021 Document type: Preprint
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