Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2

Mooij P.*, García-Arriaza J.*, Pérez P., Lázaro-Frías A., Verstrepen B.E., Böszörményi K.P., Mortier D., Fagrouch Z., Kiemenyi-Kayere G., Niphuis H., Acar R.F., Meijer L., Stammes M.A., Kondova I., Verschoor E. J., GeurtsvanKessel C.H., de Bruin E., Sikkema R. S., Luczkowiak J., Delgado R., Montenegro D., Puentes E., Rodríguez E., Bogers W.M.J.M., Koopman G., Esteban M.

* Authors have contributed equally to this work and share first authorship

Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNgamma, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials.

Printed March 2022 in Frontiers in Immunology

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Host switching pathogens, infectious outbreaks and zoonosis; a Marie Sklodowska-Curie Innovative Training Network.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 721367.