DNA vaccine protection against SARS-CoV-2 in rhesus macaques
A. Van Ry, J.D. Ventura, N.B. Mercado, R. Nityanandam, F.J.N. Lelis, M. Travers, B. Chen, D.R. Wesemann, A. Cook, Jinzhou Yu, K. McMahan, R. Brown, M.G. Lewis, J. Liu, N. Kordana, A. Chandrashekar, S. Fischinger, Armando García Schmidt, M.D. Slein, C. Loos, J.S. Burke, YongBing CHEN, E. Teow, L. Pessaint, F. Nampanya, Xiaodie He, G. Alter, Z. Li, Y. Cai, A. Dodson, M. Kirilova, A. Zuiani, D.H. Barouch, C. Jacob-Dolan, R. Zahn, H. Andersen, F. Wegmann, L.F. Maxfield, M.S. Gebre, S. Habibi, London Peter, S.H. Mahrokhian, L.H. Tostanoski, G. Dagotto, C. Atyeo, B. Finneyfrock, R.S. Baric, J.P. Nkolola, Huyun Wan, Johana Gabriela Cubías Velasco, Z. Lin, K. Blade, E.A. Bondzie, D.R. Martinez
Abstract
The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.