Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

Kevin O. Saunders (), Esther Lee, Robert Parks, David R. Martinez, 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, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Anyway B. Kapingidza, Mihai Azoitei, Longping V. Tse, Trevor D. Scobey, Rachel L. Spreng, R. Wes Rountree, C. Todd DeMarco, Thomas N. Denny, Christopher W. Woods, Elizabeth W. Petzold, Juanjie Tang, Thomas H. Oguin, Gregory D. Sempowski, Matthew Gagne, Daniel C. Douek, Mark A. Tomai, Christopher B. Fox, Robert Seder, Kevin Wiehe, Drew Weissman, Norbert Pardi, Hana Golding, Surender Khurana, Priyamvada Acharya, Hanne Andersen, Mark G. Lewis, Ian N. Moore, David C. Montefiori, Ralph S. Baric and Barton F. Haynes ()
Additional contact information
Kevin O. Saunders: Duke University School of Medicine
Esther Lee: Duke University School of Medicine
Robert Parks: Duke University School of Medicine
David R. Martinez: University of North Carolina at Chapel Hill
Dapeng Li: Duke University School of Medicine
Haiyan Chen: Duke University School of Medicine
Robert J. Edwards: Duke University School of Medicine
Sophie Gobeil: Duke University School of Medicine
Maggie Barr: Duke University School of Medicine
Katayoun Mansouri: Duke University School of Medicine
S. Munir Alam: Duke University School of Medicine
Laura L. Sutherland: Duke University School of Medicine
Fangping Cai: Duke University School of Medicine
Aja M. Sanzone: Duke University School of Medicine
Madison Berry: Duke University School of Medicine
Kartik Manne: Duke University School of Medicine
Kevin W. Bock: National Institutes of Health (NIH)
Mahnaz Minai: National Institutes of Health (NIH)
Bianca M. Nagata: National Institutes of Health (NIH)
Anyway B. Kapingidza: Duke University School of Medicine
Mihai Azoitei: Duke University School of Medicine
Longping V. Tse: University of North Carolina at Chapel Hill
Trevor D. Scobey: University of North Carolina at Chapel Hill
Rachel L. Spreng: Duke University School of Medicine
R. Wes Rountree: Duke University School of Medicine
C. Todd DeMarco: Duke University School of Medicine
Thomas N. Denny: Duke University School of Medicine
Christopher W. Woods: Duke University School of Medicine
Elizabeth W. Petzold: Duke University Medical Center
Juanjie Tang: Food and Drug Administration
Thomas H. Oguin: Duke University School of Medicine
Gregory D. Sempowski: Duke University School of Medicine
Matthew Gagne: Vaccine Research Center, NIAID, NIH
Daniel C. Douek: Vaccine Research Center, NIAID, NIH
Mark A. Tomai: Corporate Research Materials Lab, 3M Company
Christopher B. Fox: Infectious Disease Research Institute
Robert Seder: Vaccine Research Center, NIAID, NIH
Kevin Wiehe: Duke University School of Medicine
Drew Weissman: University of Pennsylvania
Norbert Pardi: University of Pennsylvania
Hana Golding: Food and Drug Administration
Surender Khurana: Food and Drug Administration
Priyamvada Acharya: Duke University School of Medicine
Hanne Andersen: BIOQUAL
Mark G. Lewis: BIOQUAL
Ian N. Moore: National Institutes of Health (NIH)
David C. Montefiori: Duke University School of Medicine
Ralph S. Baric: University of North Carolina at Chapel Hill
Barton F. Haynes: Duke University School of Medicine

Nature, 2021, vol. 594, issue 7864, 553-559

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-03594-0

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