期刊
CELL
卷 183, 期 5, 页码 1367-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.10.043
关键词
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资金
- Bill & Melinda Gates Foundation [OPP1156262, OPP1126258, OPP1159947]
- Defense Threat Reduction Agency [HDTRA1-18-1-0001]
- National Institute of General Medical Sciences [R01GM120553, R01GM099989]
- National Institute of Allergy and Infectious Diseases [DP1AI158186, HHSN272201700059C, 3U01AI42001-02S1]
- Pew Biomedical Scholars Award
- OD/NIH HHS/United States [P51 OD010425]
- Burroughs Wellcome Fund
- Fast Grants
- Animal Models Contract [HHSN272201700036I-75N93020F00001]
- University of Washington's Proteomics Resource [UWPR95794]
- North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill
- North Carolina Coronavirus Relief Fund
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP1AI158186] Funding Source: NIH RePORTER
- Bill and Melinda Gates Foundation [OPP1159947, OPP1126258] Funding Source: Bill and Melinda Gates Foundation
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.
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