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Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.
Nature. 2021 06; 594(7864):553-559.Nat

Abstract

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.

Authors+Show Affiliations

Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. kevin.saunders@duke.edu. Department of Surgery, Duke University, Durham, NC, USA. kevin.saunders@duke.edu. Department of Immunology, Duke University School of Medicine, Durham, NC, USA. kevin.saunders@duke.edu. Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA. kevin.saunders@duke.edu.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA. Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC, USA.Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC, USA.Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.Corporate Research Materials Lab, 3M Company, St Paul, MN, USA.Infectious Disease Research Institute, Seattle, WA, USA.Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Medicine, Duke University School of Medicine, Durham, NC, USA.Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD, USA.Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Surgery, Duke University, Durham, NC, USA.BIOQUAL, Rockville, MD, USA.BIOQUAL, Rockville, MD, USA.Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Department of Surgery, Duke University, Durham, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. barton.haynes@duke.edu. Department of Immunology, Duke University School of Medicine, Durham, NC, USA. barton.haynes@duke.edu. Department of Medicine, Duke University School of Medicine, Durham, NC, USA. barton.haynes@duke.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

33971664

Citation

Saunders, Kevin O., et al. "Neutralizing Antibody Vaccine for Pandemic and Pre-emergent Coronaviruses." Nature, vol. 594, no. 7864, 2021, pp. 553-559.
Saunders KO, Lee E, Parks R, et al. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature. 2021;594(7864):553-559.
Saunders, K. O., Lee, E., Parks, R., Martinez, D. R., Li, D., Chen, H., Edwards, R. J., Gobeil, S., Barr, M., Mansouri, K., Alam, S. M., Sutherland, L. L., Cai, F., Sanzone, A. M., Berry, M., Manne, K., Bock, K. W., Minai, M., Nagata, B. M., ... Haynes, B. F. (2021). Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature, 594(7864), 553-559. https://doi.org/10.1038/s41586-021-03594-0
Saunders KO, et al. Neutralizing Antibody Vaccine for Pandemic and Pre-emergent Coronaviruses. Nature. 2021;594(7864):553-559. PubMed PMID: 33971664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. AU - Saunders,Kevin O, AU - Lee,Esther, AU - Parks,Robert, AU - Martinez,David R, AU - Li,Dapeng, AU - Chen,Haiyan, AU - Edwards,Robert J, AU - Gobeil,Sophie, AU - Barr,Maggie, AU - Mansouri,Katayoun, AU - Alam,S Munir, AU - Sutherland,Laura L, AU - Cai,Fangping, AU - Sanzone,Aja M, AU - Berry,Madison, AU - Manne,Kartik, AU - Bock,Kevin W, AU - Minai,Mahnaz, AU - Nagata,Bianca M, AU - Kapingidza,Anyway B, AU - Azoitei,Mihai, AU - Tse,Longping V, AU - Scobey,Trevor D, AU - Spreng,Rachel L, AU - Rountree,R Wes, AU - DeMarco,C Todd, AU - Denny,Thomas N, AU - Woods,Christopher W, AU - Petzold,Elizabeth W, AU - Tang,Juanjie, AU - Oguin,Thomas H,3rd AU - Sempowski,Gregory D, AU - Gagne,Matthew, AU - Douek,Daniel C, AU - Tomai,Mark A, AU - Fox,Christopher B, AU - Seder,Robert, AU - Wiehe,Kevin, AU - Weissman,Drew, AU - Pardi,Norbert, AU - Golding,Hana, AU - Khurana,Surender, AU - Acharya,Priyamvada, AU - Andersen,Hanne, AU - Lewis,Mark G, AU - Moore,Ian N, AU - Montefiori,David C, AU - Baric,Ralph S, AU - Haynes,Barton F, Y1 - 2021/05/10/ PY - 2021/02/07/received PY - 2021/04/29/accepted PY - 2021/5/11/pubmed PY - 2021/7/1/medline PY - 2021/5/10/entrez SP - 553 EP - 559 JF - Nature JO - Nature VL - 594 IS - 7864 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/33971664/Neutralizing_antibody_vaccine_for_pandemic_and_pre_emergent_coronaviruses_ L2 - https://doi.org/10.1038/s41586-021-03594-0 DB - PRIME DP - Unbound Medicine ER -