Evidence map›Paper›PMID 34534459›Full record

ArticleCell reports2021

Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies.

Claudia A Jette, Alexander A Cohen, Priyanthi N P Gnanapragasam, Frauke Muecksch, Yu E Lee, Kathryn E Huey-Tubman, Fabian Schmidt, Theodora Hatziioannou, Paul D Bieniasz, Michel C Nussenzweig and 4 more

Erratum issuedAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing 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

92 citing papers in PubMed.

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  18. Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Review
  20. Article

32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Claudia A JetteDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Alexander A CohenDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Priyanthi N P GnanapragasamDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Frauke MueckschLaboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
Yu E LeeDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Kathryn E Huey-TubmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Fabian SchmidtLaboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
Theodora HatziioannouLaboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
Paul D BieniaszLaboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute.
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute.
Anthony P WestDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Jennifer R KeeffeDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: bjorkman@caltech.edu.
Christopher O BarnesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: cobarnes@caltech.edu.

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Aina E. Cohen · 2020 to 2026
$43.3M
Overcoming Host Restriction Factors to Develop Better Animal Models for HIV/AIDS.R01AI078788 · NIAID · ROCKEFELLER UNIVERSITY · PI HATZIIOANNOU, THEODORA · 2008 to 2021
$9.3M
Virology CoreP01AI138938 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2018 to 2022
$8.4M
NIAID NIH HHS P01 AI138938NIAID NIH HHS R01 AI078788NIAID NIH HHS R01AI640511NIGMS NIH HHS P30 GM133894
6 · The paper itself

Abstract

Many anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) neutralizing antibodies target the angiotensin-converting enzyme 2 (ACE2) binding site on viral spike receptor-binding domains (RBDs). Potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly emergent zoonotic sarbecoviruses and variants, but they usually show only weak neutralization potencies. Here, we characterize two class 4 anti-RBD antibodies derived from coronavirus disease 2019 (COVID-19) donors that exhibit breadth and potent neutralization of zoonotic coronaviruses and SARS-CoV-2 variants. C118-RBD and C022-RBD structures reveal orientations that extend from the cryptic epitope to occlude ACE2 binding and CDRH3-RBD main-chain H-bond interactions that extend an RBD β sheet, thus reducing sensitivity to RBD side-chain changes. A C118-spike trimer structure reveals rotated RBDs that allow access to the cryptic epitope and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.

Indexed as

Antibodies, NeutralizingAntibodies, ViralBinding SitesBroadly Neutralizing AntibodiesCOVID-19Cross ReactionsEpitopesHumansProtein BindingProtein Interaction Domains and MotifsReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesEpitopesReceptors, VirusSpike Glycoprotein, Coronaviruscoronaviruscryo-EMneutralizing antibodyreceptor-binding domainsarbecovirusSARS-CoV-2Spike trimer: structural biologyvirology: X-ray crystallography

Identifiers

PMID34534459
PMCPMC8423902

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.