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Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2

Cell, 2020-11, Vol.183 (5), p.1367-1382.e17 [Peer Reviewed Journal]

2020 The Authors ;Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. ;2020. Not withstanding the ProQuest Terms and Conditions, you may use this content in accordance with the associated terms available at https://www.elsevier.com/legal/elsevier-website-terms-and-conditions ;2020 The Authors 2020 ;ISSN: 0092-8674 ;EISSN: 1097-4172 ;DOI: 10.1016/j.cell.2020.10.043 ;PMID: 33160446

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Title:
Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2
Author: Walls, Alexandra C. ; Fiala, Brooke ; Schäfer, Alexandra ; Wrenn, Samuel ; Pham, Minh N. ; Murphy, Michael ; Tse, Longping V. ; Shehata, Laila ; O’Connor, Megan A. ; Chen, Chengbo ; Navarro, Mary Jane ; Miranda, Marcos C. ; Pettie, Deleah ; Ravichandran, Rashmi ; Kraft, John C. ; Ogohara, Cassandra ; Palser, Anne ; Chalk, Sara ; Lee, E-Chiang ; Guerriero, Kathryn ; Kepl, Elizabeth ; Chow, Cameron M. ; Sydeman, Claire ; Hodge, Edgar A. ; Brown, Brieann ; Fuller, Jim T. ; Dinnon, Kenneth H. ; Gralinski, Lisa E. ; Leist, Sarah R. ; Gully, Kendra L. ; Lewis, Thomas B. ; Guttman, Miklos ; Chu, Helen Y. ; Lee, Kelly K. ; Fuller, Deborah H. ; Baric, Ralph S. ; Kellam, Paul ; Carter, Lauren ; Pepper, Marion ; Sheahan, Timothy P. ; Veesler, David ; King, Neil P.
Subjects: Adolescent ; Adult ; Aged ; Animals ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Chlorocebus aethiops ; Cohort Studies ; computational protein design ; COVID-19 - prevention & control ; COVID-19 - virology ; COVID-19 Vaccines - immunology ; Epitopes - immunology ; Female ; HEK293 Cells ; Humans ; Macaca nemestrina ; Male ; Mice, Inbred BALB C ; Middle Aged ; nanoparticle ; Nanoparticles - chemistry ; protein ; Protein Domains - immunology ; RBD ; SARS-CoV-2 ; SARS-CoV-2 - genetics ; SARS-CoV-2 - immunology ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - immunology ; Vaccination ; vaccine ; Vero Cells ; Young Adult
Is Part Of: Cell, 2020-11, Vol.183 (5), p.1367-1382.e17
Description: 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. [Display omitted] •Two-component nanoparticle platform enabled rapid generation of SARS-CoV-2 vaccines•The RBD-nanoparticle vaccines elicit potent neutralizing antibody responses•Nanoparticle vaccine-elicited antibodies target multiple non-overlapping epitopes•The lead nanoparticle vaccine candidate is being manufactured for clinical trials Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0092-8674
EISSN: 1097-4172
DOI: 10.1016/j.cell.2020.10.043
PMID: 33160446
Source: Coronavirus Research Database

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Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2

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