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Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses - Nature.com

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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.

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Affiliations

  1. Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA

    Kevin O. Saunders, Esther Lee, Robert Parks, Dapeng Li, Haiyan Chen, Robert J. Edwards, Sophie Gobeil, Maggie Barr, Katayoun Mansouri, S. Munir Alam, Laura L. Sutherland, Fangping Cai, Aja M. Sanzone, Madison Berry, Kartik Manne, Anyway B. Kapingidza, Mihai Azoitei, Rachel L. Spreng, R. Wes Rountree, C. Todd DeMarco, Thomas N. Denny, Christopher W. Woods, Thomas H. Oguin III, Gregory D. Sempowski, Kevin Wiehe, Priyamvada Acharya, David C. Montefiori & Barton F. Haynes

  2. Department of Surgery, Duke University, Durham, NC, USA

    Kevin O. Saunders, Priyamvada Acharya & David C. Montefiori

  3. Department of Immunology, Duke University School of Medicine, Durham, NC, USA

    Kevin O. Saunders & Barton F. Haynes

  4. Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA

    Kevin O. Saunders

  5. Department of Medicine, Duke University School of Medicine, Durham, NC, USA

    Esther Lee, Robert Parks, Dapeng Li, Haiyan Chen, Robert J. Edwards, Sophie Gobeil, Maggie Barr, Katayoun Mansouri, S. Munir Alam, Laura L. Sutherland, Fangping Cai, Aja M. Sanzone, Madison Berry, Kartik Manne, Anyway B. Kapingidza, Mihai Azoitei, Rachel L. Spreng, R. Wes Rountree, C. Todd DeMarco, Thomas N. Denny, Christopher W. Woods, Thomas H. Oguin III, Gregory D. Sempowski, Kevin Wiehe & Barton F. Haynes

  6. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    David R. Martinez, Longping V. Tse, Trevor D. Scobey & Ralph S. Baric

  7. Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata & Ian N. Moore

  8. Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC, USA

    Christopher W. Woods & Elizabeth W. Petzold

  9. Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD, USA

    Juanjie Tang, Hana Golding & Surender Khurana

  10. Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA

    Matthew Gagne, Daniel C. Douek & Robert Seder

  11. Corporate Research Materials Lab, 3M Company, St Paul, MN, USA

    Mark A. Tomai

  12. Infectious Disease Research Institute, Seattle, WA, USA

    Christopher B. Fox

  13. Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Drew Weissman & Norbert Pardi

  14. BIOQUAL, Rockville, MD, USA

    Hanne Andersen & Mark G. Lewis

Authors
  1. Kevin O. Saunders
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  2. Esther Lee
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  3. Robert Parks
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  4. David R. Martinez
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  5. Dapeng Li
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  6. Haiyan Chen
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  7. Robert J. Edwards
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  8. Sophie Gobeil
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  9. Maggie Barr
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  10. Katayoun Mansouri
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  11. S. Munir Alam
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  12. Laura L. Sutherland
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  13. Fangping Cai
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  14. Aja M. Sanzone
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  15. Madison Berry
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  16. Kartik Manne
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  17. Kevin W. Bock
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  18. Mahnaz Minai
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  19. Bianca M. Nagata
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  20. Anyway B. Kapingidza
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  21. Mihai Azoitei
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  22. Longping V. Tse
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  23. Trevor D. Scobey
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  24. Rachel L. Spreng
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  25. R. Wes Rountree
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  26. C. Todd DeMarco
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  27. Thomas N. Denny
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  28. Christopher W. Woods
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  29. Elizabeth W. Petzold
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  30. Juanjie Tang
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  31. Thomas H. Oguin III
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  32. Gregory D. Sempowski
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  33. Matthew Gagne
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  34. Daniel C. Douek
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  35. Mark A. Tomai
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  36. Christopher B. Fox
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  37. Robert Seder
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  38. Kevin Wiehe
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  39. Drew Weissman
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  40. Norbert Pardi
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  41. Hana Golding
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  42. Surender Khurana
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  43. Priyamvada Acharya
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  44. Hanne Andersen
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  45. Mark G. Lewis
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  46. Ian N. Moore
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  47. David C. Montefiori
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  48. Ralph S. Baric
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  49. Barton F. Haynes
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Corresponding authors

Correspondence to Kevin O. Saunders or Barton F. Haynes.

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Saunders, K.O., Lee, E., Parks, R. et al. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature (2021). https://ift.tt/3vVRl5e

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