SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys
Saunders, K. O.; Lee, E.; Parks, R.; Martinez, D. R.; Li, D.; Chen, H.; Edwards, R. J.; Gobeil, S. M. C.; Barr, M.; Mansouri, K.; Alam, S. M.; Sutherland, L. L.; Cai, F.; Sanzone, A.; Berry, M.; Manne, K.; Kapingidza, A. B.; Azoitei, M.; Tse, L. V.; Scobey, T. D.; Spreng, R.; Rountree, R. W.; DeMarco, C. T.; Denny, T. N.; Woods, C. W.; Petzold, E. W.; Oguin, T. H.; Sempowski, G. D.; Gagne, M.; Douek, D. C.; Tomai, M. A.; Fox, C. B.; Seder, R.; Wiehe, K.; Weissman, D.; Pardi, N.; Acharya, P.; Andersen, H.; Lewis, M. G.; Moore, I. N.; Montefiori, D. C.; Baric, R. S.; Haynes, B. F.
Show abstract
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.
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