Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination
| Autor: | Leonard Limpinsel, Berislav Bošnjak, Anke Werner, Inga Sandrock, Clemens M. Wendtner, Nisreen M.A. Okba, Sylvia Jany, Lucie Sauerhering, Alexandra Kupke, Joerg C. Schmidt, Cornelius Rohde, Astrid Freudenstein, M Seilmaier, Asisa Volz, Wolfgang Guggemos, Reinhold Foerster, Stephan Becker, Jan Hendrik Schwarz, Bart L. Haagmans, Georgia Kalodimou, Elke R. Duell, Michael Kluever, Sandro Halwe, Liangliang Nan, Gerd Sutter, Michelle Gellhorn, Katrin Printz, Alina Tscherne |
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| Rok vydání: | 2021 |
| Předmět: |
Ebola virus
business.industry Middle East respiratory syndrome coronavirus viruses fungi Vector vaccine medicine.disease_cause complex mixtures Virology Virus body regions Vaccination chemistry.chemical_compound chemistry medicine Vaccinia skin and connective tissue diseases business Smallpox vaccine Coronavirus |
| DOI: | 10.1101/2021.01.09.426032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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