Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Saunders, Kevin O; Lee, Esther; Parks, Robert; Martinez, David R; Li, Dapeng; Chen, Haiyan; Edwards, Robert J; Gobeil, Sophie; Barr, Maggie; Mansouri, Katayoun; Alam, S Munir; Sutherland, Laura L; Cai, Fangping; Sanzone, Aja M; Berry, Madison; Manne, Kartik; Bock, Kevin W; Minai, Mahnaz; Nagata, Bianca M; Kapingidza, Anyway B; Azoitei, Mihai; Tse, Longping V; Scobey, Trevor D; Spreng, Rachel L; Rountree, R Wes; DeMarco, C Todd; Denny, Thomas N; Woods, Christopher W; Petzold, Elizabeth W; Tang, Juanjie; Oguin, Thomas H; Sempowski, Gregory D; Gagne, Matthew; Douek, Daniel C; Tomai, Mark A; Fox, Christopher B; Seder, Robert; Wiehe, Kevin; Weissman, Drew; Pardi, Norbert; Golding, Hana; Khurana, Surender; Acharya, Priyamvada; Andersen, Hanne; Lewis, Mark G; Moore, Ian N; Montefiori, David C; Baric, Ralph S; Haynes, Barton F

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and the SARS-CoV-2 pandemic1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that macaque immunization with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052/Alum elicited cross-neutralizing antibody (cross-nAb) responses against batCoVs, SARS-CoV-1, SARS-CoV-2, and SARS-CoV-2 variants B.1.1.7, P.1, and B.1.351. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization ID50 titer of 47,216, and protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD also induced SARS-CoV-1 and batCoV cross-nAbs, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV vaccines.