COVID-19 Vaccine Candidates Based on Modified Vaccinia Virus Ankara Expressing the SARS-CoV-2 Spike Protein Induce Robust T- and B-Cell Immune Responses and Full Efficacy in Mice
Juan García‐Arriaza, Urtzi Garaigorta, Patricia Pérez, Adrián Lázaro-Frías, Carmen Zamora, Pablo Gastaminza, Carlos del Fresno, José M. Casasnovas, Carlos Óscar S. Sorzano, David Sancho, Mariano Estéban
Abstract
The continuous dissemination of the novel emerging SARS-CoV-2 virus, with more than 78 million infected cases worldwide and higher than 1,700,000 deaths as of December 23, 2020, highlights the urgent need for the development of novel vaccines against COVID-19. With this aim, we have developed novel vaccine candidates based on the poxvirus modified vaccinia virus Ankara (MVA) strain expressing the full-length SARS-CoV-2 spike (S) protein, and we have evaluated their immunogenicity in mice using DNA/MVA or MVA/MVA prime/boost immunization protocols. The results showed the induction of a potent S-specific T-cell response and high titers of neutralizing antibodies. Remarkably, humanized K18-hACE2 mice immunized with one or two doses of the MVA-based vaccine were 100% protected from SARS-CoV-2 lethality. Moreover, two doses of the vaccine prevented virus replication in lungs. Our findings prove the robust immunogenicity and efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic.