Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

 Kevin O. Saunders1,2,3,4 ✉, Esther Lee1,5, Robert Parks1,5, David R. Martinez6 , Dapeng Li1,5, Haiyan Chen1,5, Robert J. Edwards1,5, Sophie Gobeil1,5, Maggie Barr1,5, Katayoun Mansouri1,5, S. Munir Alam1,5, Laura L. Sutherland1,5, Fangping Cai1,5, Aja M. Sanzone1,5, Madison Berry1,5, Kartik Manne1,5, Kevin W. Bock7 , Mahnaz Minai7 , Bianca M. Nagata7 , Anyway B. Kapingidza1,5, Mihai Azoitei1,5, Longping V. Tse6 , Trevor D. Scobey6 , Rachel L. Spreng1,5, R. Wes Rountree1,5, C. Todd DeMarco1,5, Thomas N. Denny1,5, Christopher W. Woods1,5,8, Elizabeth W. Petzold8 , Juanjie Tang9 , Thomas H. Oguin III1,5, Gregory D. Sempowski1,5, Matthew Gagne10, Daniel C. Douek10, Mark A. Tomai11, Christopher B. Fox12, Robert Seder10, Kevin Wiehe1,5, Drew Weissman13, Norbert Pardi13, Hana Golding9 , Surender Khurana9 , Priyamvada Acharya1,2, Hanne Andersen14, Mark G. Lewis14, Ian N. Moore7 , David C. Montefiori1,2, Ralph S. Baric6 & Barton F. Haynes

DOI: https://doi.org/10.1038/s41586-021-03594-0

Abstract

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-modifed 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.

https://www.nature.com/articles/s41586-021-03594-0_reference.pdf