Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

Dapeng Li, David R. Martinez, Alexandra Schäfer, Haiyan Chen, Maggie Barr, Laura L. Sutherland, Esther Lee, Robert Parks, Dieter Mielke, Whitney Edwards, Amanda Newman, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Matthew Gagne, Daniel C. Douek, C. Todd DeMarco, Thomas N. Denny, Thomas H. Oguin, Alecia Brown, Wes Rountree, Yunfei Wang, Katayoun Mansouri, Robert J. Edwards, Guido Ferrari, Gregory D. Sempowski, Amanda Eaton, Juanjie Tang, Derek W. Cain, Sampa Santra, Norbert Pardi, Drew Weissman, Mark A. Tomai, Christopher B. Fox, Ian N. Moore, Hanne Andersen, Mark G. Lewis, Hana Golding, Robert Seder, Surender Khurana, Ralph S. Baric, David C. Montefiori, Kevin O. Saunders () and Barton F. Haynes ()
Additional contact information
Dapeng Li: Duke University School of Medicine
David R. Martinez: University of North Carolina at Chapel Hill
Alexandra Schäfer: University of North Carolina at Chapel Hill
Haiyan Chen: Duke University School of Medicine
Maggie Barr: Duke University School of Medicine
Laura L. Sutherland: Duke University School of Medicine
Esther Lee: Duke University School of Medicine
Robert Parks: Duke University School of Medicine
Dieter Mielke: Duke University School of Medicine
Whitney Edwards: Duke University School of Medicine
Amanda Newman: Duke University School of Medicine
Kevin W. Bock: National Institutes of Health
Mahnaz Minai: National Institutes of Health
Bianca M. Nagata: National Institutes of Health
Matthew Gagne: National Institutes of Health
Daniel C. Douek: National Institutes of Health
C. Todd DeMarco: Duke University School of Medicine
Thomas N. Denny: Duke University School of Medicine
Thomas H. Oguin: Duke University School of Medicine
Alecia Brown: Duke University School of Medicine
Wes Rountree: Duke University School of Medicine
Yunfei Wang: Duke University School of Medicine
Katayoun Mansouri: Duke University School of Medicine
Robert J. Edwards: Duke University School of Medicine
Guido Ferrari: Duke University School of Medicine
Gregory D. Sempowski: Duke University School of Medicine
Amanda Eaton: Duke University School of Medicine
Juanjie Tang: Food and Drug Administration
Derek W. Cain: Duke University School of Medicine
Sampa Santra: Beth Israel Deaconess Medical Center
Norbert Pardi: University of Pennsylvania
Drew Weissman: University of Pennsylvania
Mark A. Tomai: 3M Company
Christopher B. Fox: Infectious Disease Research Institute
Ian N. Moore: National Institutes of Health
Hanne Andersen: BIOQUAL
Mark G. Lewis: BIOQUAL
Hana Golding: Food and Drug Administration
Robert Seder: National Institutes of Health
Surender Khurana: Food and Drug Administration
Ralph S. Baric: University of North Carolina at Chapel Hill
David C. Montefiori: Duke University School of Medicine
Kevin O. Saunders: Duke University School of Medicine
Barton F. Haynes: Duke University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants.

Date: 2022
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DOI: 10.1038/s41467-022-33985-4

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