Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • June 2021

Published In

Volume / Issue

  • 594 / 7864

Start / End Page

  • 553 - 559

PubMed ID

  • 33971664

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/s41586-021-03594-0

Language

  • eng

Conference Location

  • England