Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

Abstract

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and the SARS-CoV-2 pandemic^1–4. 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.