Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice
Adrián Lázaro-Frías,
Patricia Pérez,
Carmen Zamora,
Pedro J. Sánchez-Cordón,
María Guzmán,
Joanna Luczkowiak,
Rafael Delgado,
José M. Casasnovas,
Mariano Esteban,
Juan García-Arriaza
Affiliations
Adrián Lázaro-Frías
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)
Patricia Pérez
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)
Carmen Zamora
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)
Pedro J. Sánchez-Cordón
Pathology Department, Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Científicas (CSIC)
María Guzmán
Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)
Joanna Luczkowiak
Instituto de Investigación Hospital Universitario 12 de Octubre (imas12)
Rafael Delgado
Instituto de Investigación Hospital Universitario 12 de Octubre (imas12)
José M. Casasnovas
Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)
Mariano Esteban
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)
Juan García-Arriaza
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)
Abstract Two doses of the MVA-CoV2-S vaccine candidate expressing the SARS-CoV-2 spike (S) protein protected K18-hACE2 transgenic mice from a lethal dose of SARS-CoV-2. This vaccination regimen prevented virus replication in the lungs, reduced lung pathology, and diminished levels of pro-inflammatory cytokines. High titers of IgG antibodies against S and receptor-binding domain (RBD) proteins and of neutralizing antibodies were induced against parental virus and variants of concern, markers that correlated with protection. Similar SARS-CoV-2-specific antibody responses were observed at prechallenge and postchallenge in the two-dose regimen, while the single-dose treatment does not avoid vaccine breakthrough infection. All vaccinated animals survived infection and were also protected to SARS-CoV-2 reinfection. Furthermore, two MVA-CoV2-S doses induced long-term memory S-specific humoral and cellular immune responses in C57BL/6 mice, 6 months after immunization. The efficacy and immunological benefits of the MVA-CoV2-S vaccine candidate against COVID-19 supports its consideration for human clinical trials.
