Evidence map›Paper›PMID 32817941›Full record

ArticlebioRxiv : the preprint server for biology2020

Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2.

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 and 31 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 59 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

41 authors at 3 institutions in 3 countries.

Alexandra C WallsDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Brooke FialaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Alexandra SchäferDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Samuel WrennDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Minh N PhamDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Michael MurphyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Longping V TseDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Laila ShehataDepartment of Immunology, University of Washington, Seattle, WA 98109, USA.
Megan A O'ConnorDepartment of Microbiology, University of Washington, Seattle, WA 98109, USA.
Chengbo ChenDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Mary Jane NavarroDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Marcos C MirandaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Deleah PettieDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Rashmi RavichandranDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
John C KraftDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cassandra OgoharaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Anne PalserKymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.
Sara ChalkKymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.
E-Chiang LeeKymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.
Elizabeth KeplDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cameron M ChowDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Claire SydemanDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Edgar A HodgeDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Brieann BrownDepartment of Microbiology, University of Washington, Seattle, WA 98109, USA.
Jim T FullerDepartment of Microbiology, University of Washington, Seattle, WA 98109, USA.
Kenneth H DinnonDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Lisa E GralinskiDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Sarah R LeistDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Kendra L GullyDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Thomas B LewisDepartment of Microbiology, University of Washington, Seattle, WA 98109, USA.
Miklos GuttmanDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Helen Y ChuDepartment of Medicine, University of Washington, Seattle, WA 98109, USA.
Kelly K LeeDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Deborah H FullerDepartment of Microbiology, University of Washington, Seattle, WA 98109, USA.
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Paul KellamKymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.
Lauren CarterDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Marion PepperDepartment of Immunology, University of Washington, Seattle, WA 98109, USA.
Timothy P SheahanDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
David VeeslerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Neil P KingDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
University of Washington · USUniversity of North Carolina at Chapel Hill · USKymab (United Kingdom) · GB

Funding

Waters ACQUITY UPLC M-Class with NanoLockSpray ionization sourceR01GM099989 · NIGMS · UNIVERSITY OF WASHINGTON · PI LEE, KELLY KEISEN · 2012 to 2020
$3.5M
Basic Training at the Intersection of Innate and Adaptive Immunity in DiseaseT32AI106677 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL, GOVERMAN, JOAN M · 2013 to 2022
$2.1M
Structural Studies of Coronavirus Fusion ProteinsR01GM120553 · NIGMS · UNIVERSITY OF WASHINGTON · PI VEESLER, DAVID · 2016 to 2020
$1.7M
NIAID NIH HHS HHSN272201700059CNIAID NIH HHS T32 AI106677NIGMS NIH HHS R01 GM099989NIGMS NIH HHS R01 GM120553
6 · The paper itself

Abstract

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.

Identifiers

PMID32817941
PMCPMC7430571
OpenAlexW3048499980

What OpenQuestion holds

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LicenceCC BY-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.