Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

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  • Saunders, K.O.
    • Other Affiliation: Duke University School of Medicine
  • Lee, E.
    • Other Affiliation: Duke University School of Medicine
  • Parks, R.
    • Other Affiliation: Duke University School of Medicine
  • Martinez, D.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Li, D.
    • Other Affiliation: Duke University School of Medicine
  • Chen, H.
    • Other Affiliation: Duke University School of Medicine
  • Edwards, R.J.
    • Other Affiliation: Duke University School of Medicine
  • Gobeil, S.
    • Other Affiliation: Duke University School of Medicine
  • Barr, M.
    • Other Affiliation: Duke University School of Medicine
  • Mansouri, K.
    • Other Affiliation: Duke University School of Medicine
  • Alam, S.M.
    • Other Affiliation: Duke University School of Medicine
  • Sutherland, L.L.
    • Other Affiliation: Duke University School of Medicine
  • Cai, F.
    • Other Affiliation: Duke University School of Medicine
  • Sanzone, A.M.
    • Other Affiliation: Duke University School of Medicine
  • Berry, M.
    • Other Affiliation: Duke University School of Medicine
  • Manne, K.
    • Other Affiliation: Duke University School of Medicine
  • Bock, K.W.
    • Other Affiliation: National Institute of Allergy and Infectious Diseases
  • Minai, M.
    • Other Affiliation: National Institute of Allergy and Infectious Diseases
  • Nagata, B.M.
    • Other Affiliation: National Institute of Allergy and Infectious Diseases
  • Kapingidza, A.B.
    • Other Affiliation: Duke University School of Medicine
  • Azoitei, M.
    • Other Affiliation: Duke University School of Medicine
  • Tse, L.V.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Scobey, T.D.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Spreng, R.L.
    • Other Affiliation: Duke University School of Medicine
  • Rountree, R.W.
    • Other Affiliation: Duke University School of Medicine
  • DeMarco, C.T.
    • Other Affiliation: Duke University School of Medicine
  • Denny, T.N.
    • Other Affiliation: Duke University School of Medicine
  • Woods, C.W.
    • Other Affiliation: Duke University School of Medicine
  • Petzold, E.W.
    • Other Affiliation: Duke University Medical Center
  • Tang, J.
    • Other Affiliation: Food and Drug Administration
  • Oguin, T.H., III
    • Other Affiliation: Duke University School of Medicine
  • Sempowski, G.D.
    • Other Affiliation: Duke University School of Medicine
  • Gagne, M.
    • Other Affiliation: National Institute of Allergy and Infectious Diseases
  • Douek, D.C.
    • Other Affiliation: National Institute of Allergy and Infectious Diseases
  • Tomai, M.A.
    • Other Affiliation: 3M Company
  • Fox, C.B.
    • Other Affiliation: Infectious Disease Research Institute
  • Seder, R.
    • Other Affiliation: National Institute of Allergy and Infectious Diseases
  • Wiehe, K.
    • Other Affiliation: Duke University School of Medicine
  • Weissman, D.
    • Other Affiliation: University of Pennsylvania
  • Pardi, N.
    • Other Affiliation: University of Pennsylvania
  • Golding, H.
    • Other Affiliation: Food and Drug Administration
  • Khurana, S.
    • Other Affiliation: Food and Drug Administration
  • Acharya, P.
    • Other Affiliation: Duke University School of Medicine
  • Andersen, H., BIOQUAL, Rockville, MD, United States
  • Lewis, M.G., BIOQUAL, Rockville, MD, United States
  • Moore, I.N.
    • Other Affiliation: National Institute of Allergy and Infectious Diseases
  • Montefiori, D.C.
    • Other Affiliation: Duke University School of Medicine
  • Baric, R.S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Haynes, B.F.
    • Other Affiliation: Duke University School of Medicine
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.
Date of publication
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Nature
Version
  • Postprint
ISSN
  • 0028-0836
Publisher
  • Nature Research

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