Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice

Adrián Lázaro-Frías,María Guzmán,Carmen Zamora,Mariano Esteban,Patricia Pérez,Rafael Delgado,Joanna Luczkowiak,Juan García-Arriaza,Pedro J Sánchez-Cordón,José M Casasnovas

doi:10.1038/s41541-022-00440-w

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.

Highlights

The COVID-19 pandemic, responsible for one of the major tragedies caused by an infectious agent in the course of one year, outweighs the human deaths by other infectious diseases
We further evaluated in detail the efficacy triggered after vaccination with one or two doses of modified vaccinia virus Ankara (MVA)-CoV2-S, through analysis after SARSCoV-2 infection of viral load, histopathology, and proinflammatory cytokine expression levels in lung samples
Changes in body weight and mortality after SARS-CoV-2 infection were previously reported and showed that all mice vaccinated with two doses of MVA-CoV2-S did not lose body weight and survived, whereas mice immunized with one dose of MVA-CoV2-S lost body weight during the first 4 days postchallenge, but they recovered and survived[5]

Summary

Introduction

The COVID-19 pandemic, responsible for one of the major tragedies caused by an infectious agent in the course of one year (about 238 million infections and 4.8 million deaths by October 2021), outweighs the human deaths by other infectious diseases. The most advanced vaccines in mass vaccination are based on adenovirus vectors (AstraZeneca, Janssen) and on mRNA (Pfizer/BioNTech and Moderna). It is remarkable the high efficacy of these vaccines, which ranges from 62-95% protection against virus infection and/or clinical disease[1,2,3]. We and others have described the advantage of the poxvirus vector modified vaccinia virus Ankara (MVA) as an immunizing agent against SARSCoV-2, probing high immunogenicity and efficacy in mouse and macaque models[4,5,6,7,8]. One or two doses of MVA-CoV2-S controlled morbidity (weight loss) and mortality caused by SARSCoV-2 infection in K18-hACE2 transgenic mice, being the two-dose regimen the most effective[5]

Methods

Results

Conclusion