SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys.
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.
Saunders, KO; Lee, E; Parks, R; Martinez, DR; Li, D; Chen, H; Edwards, RJ; Gobeil, S; Barr, M; Mansouri, K; Alam, SM; Sutherland, LL; Cai, F; Sanzone, AM; Berry, M; Manne, K; Kapingidza, AB; Azoitei, M; Tse, LV; Scobey, TD; Spreng, RL; Rountree, RW; DeMarco, CT; Denny, TN; Woods, CW; Petzold, EW; Oguin, TH; Sempowski, GD; Gagne, M; Douek, DC; Tomai, MA; Fox, CB; Seder, R; Wiehe, K; Weissman, D; Pardi, N; Acharya, P; Andersen, H; Lewis, MG; Moore, IN; Montefiori, DC; Baric, RS; Haynes, BF
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