Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.
Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.
Azoitei, Mihai Luchian
Denny, Thomas Norton
Haynes, Barton Ford
Montefiori, David Charles
Saunders, Kevin O'Neil
Sempowski, Gregory David
Wiehe, Kevin J
Woods, Christopher Wildrick
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; Bock, KW; Minai, M; Nagata, BM; Kapingidza, AB; Azoitei, M; Tse, LV; Scobey, TD; Spreng, RL; Rountree, RW; DeMarco, CT; Denny, TN; Woods, CW; Petzold, EW; Tang, J; Oguin, TH; Sempowski, GD; Gagne, M; Douek, DC; Tomai, MA; Fox, CB; Seder, R; Wiehe, K; Weissman, D; Pardi, N; Golding, H; Khurana, S; Acharya, P; Andersen, H; Lewis, MG; Moore, IN; Montefiori, DC; Baric, RS; Haynes, BF
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