Evidence map›Paper›PMID 33758839›Full record

ArticlebioRxiv : the preprint server for biology2021

Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.

Alexandra C Walls, Marcos C Miranda, Minh N Pham, Alexandra Schäfer, Allison Greaney, Prabhu S Arunachalam, Mary-Jane Navarro, M Alejandra Tortorici, Kenneth Rogers, Megan A O'Connor and 32 more

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

Article in bioRxiv : the preprint server for biology, 2021. 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, 39 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

42 authors at 10 institutions in 3 countries.

Alexandra C WallsDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Marcos C MirandaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Minh N PhamDepartment 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.
Allison GreaneyBasic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Prabhu S ArunachalamInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Mary-Jane NavarroDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
M Alejandra TortoriciDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Kenneth RogersNew Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, 70560 USA.
Megan A O'ConnorWashington National Primate Research Center, Seattle, WA 98121, USA.
Lisa ShireffNew Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, 70560 USA.
Douglas E FerrellNew Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, 70560 USA.
Natalie BrunetteDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Elizabeth KeplDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
John BowenDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Samantha K ZepedaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Tyler StarrBasic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Ching-Lin HsiehDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Brooke FialaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Samuel WrennDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Deleah PettieDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Claire SydemanDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Max JohnsonDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Alyssa BlackstoneDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Rashmi RavichandranDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cassandra OgoharaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Lauren CarterDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Sasha W TillesDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Rino RappuoliGSK, Siena, Italy.
Derek T O'HaganGSK, Rockville, MD, USA.
Robbert Van Der MostGSK, Rixensart, Belgium.
Wesley C Van VoorhisDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Jason S McLellanDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Harry KleanthousBill & Melinda Gates Foundation, Seattle, WA 98109, USA.
Timothy P SheahanDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Deborah H FullerWashington National Primate Research Center, Seattle, WA 98121, USA.
Francois VillingerNew Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, 70560 USA.
Jesse BloomBasic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bali PulendranInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Ralph BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Neil KingDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
David VeeslerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
University of Washington · USUniversity of Louisiana at Lafayette · USUniversity of North Carolina at Chapel Hill · USStanford University · USThe University of Texas at Austin · USCentre National de la Recherche Scientifique · FRFred Hutch Cancer Center · USGates Foundation · USGlaxoSmithKline (Belgium) · BEGlaxoSmithKline (United States) · US

Funding

University of Washington Arboviral Research Network (UWARN)U01AI151698 · NIAID · UNIVERSITY OF WASHINGTON · PI Michael Gale, PETER MACGARR RABINOWITZ · 2020 to 2026
$13.3M
Unraveling the bat humoral immune response against zoonotic viruses to guide the design of next-generation therapeuticsDP1AI158186 · NIAID · UNIVERSITY OF WASHINGTON · PI VEESLER, DAVID · 2020 to 2024
$5.4M
Structure, Function and Antigenicity of Coronavirus Spike ProteinsR01AI127521 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI MCLELLAN, JASON SCOTT, WARD, ANDREW BARRETT · 2017 to 2021
$3.1M
Structural Studies of Coronavirus Fusion ProteinsR01GM120553 · NIGMS · UNIVERSITY OF WASHINGTON · PI VEESLER, DAVID · 2016 to 2020
$1.7M
NIAID NIH HHS DP1 AI158186NIAID NIH HHS HHSN272201700059CNIAID NIH HHS R01 AI127521NIAID NIH HHS U01 AI151698NIGMS NIH HHS R01 GM120553
6 · The paper itself

Abstract

Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies. We benchmarked NHP serum neutralizing activity elicited by RBD-NP against a lead prefusion-stabilized SARS-CoV-2 spike immunogen using a panel of single-residue spike mutants detected in clinical isolates as well as the B.1.1.7 and B.1.351 variants of concern. Polyclonal antibodies elicited by both vaccines are resilient to most RBD mutations tested, but the E484K substitution has similar negative consequences for neutralization, and exhibit modest but comparable neutralization breadth against distantly related sarbecoviruses. We demonstrate that mosaic and cocktail sarbecovirus RBD-NPs elicit broad sarbecovirus neutralizing activity, including against the SARS-CoV-2 B.1.351 variant, and protect mice against severe SARS-CoV challenge even in the absence of the SARS-CoV RBD in the vaccine. This study provides proof of principle that sarbecovirus RBD-NPs induce heterotypic protection and enables advancement of broadly protective sarbecovirus vaccines to the clinic.

Identifiers

PMID33758839
PMCPMC7986998
OpenAlexW3138733564

What OpenQuestion holds

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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.