• Alexandra C Walls, Brooke Fiala, Alexandra Schäfer, Samuel Wrenn, Minh N Pham, Michael Murphy, Longping V Tse, Laila Shehata, Megan A O'Connor, Chengbo Chen, Mary Jane Navarro, Marcos C Miranda, Deleah Pettie, Rashmi Ravichandran, John C Kraft, Cassandra Ogohara, Anne Palser, Sara Chalk, E-Chiang Lee, Kathryn Guerriero, Elizabeth Kepl, Cameron M Chow, Claire Sydeman, Edgar A Hodge, Brieann Brown, Jim T Fuller, Kenneth H Dinnon, Lisa E Gralinski, Sarah R Leist, Kendra L Gully, Thomas B Lewis, Miklos Guttman, Helen Y Chu, Kelly K Lee, Deborah H Fuller, Ralph S Baric, Paul Kellam, Lauren Carter, Marion Pepper, Timothy P Sheahan, David Veesler, and Neil P King.
• Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
• Cell. 2020 Nov 25; 183 (5): 1367-1382.e17.

AbstractA 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.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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