Nature
. 2021 May 10.
doi: 10.1038/s41586-021-03594-0. Online ahead of print.
Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses
Kevin O Saunders 1 2 3 4 , Esther Lee 5 6 , Robert Parks 5 6 , David R Martinez 7 , Dapeng Li 5 6 , Haiyan Chen 5 6 , Robert J Edwards 5 6 , Sophie Gobeil 5 6 , Maggie Barr 5 6 , Katayoun Mansouri 5 6 , S Munir Alam 5 6 , Laura L Sutherland 5 6 , Fangping Cai 5 6 , Aja M Sanzone 5 6 , Madison Berry 5 6 , Kartik Manne 5 6 , Kevin W Bock 8 , Mahnaz Minai 8 , Bianca M Nagata 8 , Anyway B Kapingidza 5 6 , Mihai Azoitei 5 6 , Longping V Tse 7 , Trevor D Scobey 7 , Rachel L Spreng 5 6 , R Wes Rountree 5 6 , C Todd DeMarco 5 6 , Thomas N Denny 5 6 , Christopher W Woods 5 6 9 , Elizabeth W Petzold 9 , Juanjie Tang 10 , Thomas H Oguin 3rd 5 6 , Gregory D Sempowski 5 6 , Matthew Gagne 11 , Daniel C Douek 11 , Mark A Tomai 12 , Christopher B Fox 13 , Robert Seder 11 , Kevin Wiehe 5 6 , Drew Weissman 14 , Norbert Pardi 14 , Hana Golding 10 , Surender Khurana 10 , Priyamvada Acharya 5 15 , Hanne Andersen 16 , Mark G Lewis 16 , Ian N Moore 8 , David C Montefiori 5 15 , Ralph S Baric 7 , Barton F Haynes 17 18 19
Affiliations
- PMID: 33971664
- DOI: 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-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.