SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

• Published in: bioRxiv
• Main Authors: 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, 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, 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, Acharya, Priyamvada, Andersen, Hanne, Lewis, Mark G, Moore, Ian N, Montefiori, David C, Baric, Ralph S, Haynes, Barton F
• Format: Journal Article Paper
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 17.02.2021
• Subjects: Coronaviruses; Pandemics; Severe acute respiratory syndrome coronavirus 2; Vaccination
• DOI: 10.1101/2021.02.17.431492

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, 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 nanoparticle vaccines.