Imperial College London
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ProfessorPaulKellam

Faculty of Medicine, Department of Infectious Disease

Professor of Virus Genomics
 
 
 
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Contact

 

p.kellam

 
 
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Location

 

460Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Walls:2020:10.1101/2020.08.11.247395,
author = {Walls, AC and Fiala, B and Schäfer, A and Wrenn, S and Pham, MN and Murphy, M and Tse, LV and Shehata, L and O'Connor, MA and Chen, C and Navarro, MJ and Miranda, MC and Pettie, D and Ravichandran, R and Kraft, JC and Ogohara, C and Palser, A and Chalk, S and Lee, E-C and Kepl, E and Chow, CM and Sydeman, C and Hodge, EA and Brown, B and Fuller, JT and Dinnon, KH and Gralinski, LE and Leist, SR and Gully, KL and Lewis, TB and Guttman, M and Chu, HY and Lee, KK and Fuller, DH and Baric, RS and Kellam, P and Carter, L and Pepper, M and Sheahan, TP and Veesler, D and King, NP},
doi = {10.1101/2020.08.11.247395},
title = {Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2.},
url = {http://dx.doi.org/10.1101/2020.08.11.247395},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, 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 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly 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 protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.
AU  - Walls,AC
AU  - Fiala,B
AU  - Schäfer,A
AU  - Wrenn,S
AU  - Pham,MN
AU  - Murphy,M
AU  - Tse,LV
AU  - Shehata,L
AU  - O'Connor,MA
AU  - Chen,C
AU  - Navarro,MJ
AU  - Miranda,MC
AU  - Pettie,D
AU  - Ravichandran,R
AU  - Kraft,JC
AU  - Ogohara,C
AU  - Palser,A
AU  - Chalk,S
AU  - Lee,E-C
AU  - Kepl,E
AU  - Chow,CM
AU  - Sydeman,C
AU  - Hodge,EA
AU  - Brown,B
AU  - Fuller,JT
AU  - Dinnon,KH
AU  - Gralinski,LE
AU  - Leist,SR
AU  - Gully,KL
AU  - Lewis,TB
AU  - Guttman,M
AU  - Chu,HY
AU  - Lee,KK
AU  - Fuller,DH
AU  - Baric,RS
AU  - Kellam,P
AU  - Carter,L
AU  - Pepper,M
AU  - Sheahan,TP
AU  - Veesler,D
AU  - King,NP
DO  - 10.1101/2020.08.11.247395
PY  - 2020///
TI  - Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2.
UR  - http://dx.doi.org/10.1101/2020.08.11.247395
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32817941
ER  -
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