Evidence map›Paper›PMID 33948592›Full record

ArticlebioRxiv : the preprint server for biology2021

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

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. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Claudia A Jette *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Alexander A Cohen *Division 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.
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.
Theodora HatziioannouLaboratory of Retrovirology, The Rockefeller University, New York, NY 10065.
Paul D BieniaszLaboratory of Retrovirology, The Rockefeller University, New York, NY 10065.
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
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.
Christopher O BarnesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
California Institute of Technology · USRockefeller University · USHoward Hughes Medical Institute · US

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 AI078788NIGMS NIH HHS P30 GM133894
6 · The paper itself

Abstract

Many anti-SARS-CoV-2 neutralizing antibodies target the ACE2-binding site on viral spike receptor-binding domains (RBDs). The most 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 usually show only weak neutralization potencies. We characterized two class 4 anti-RBD antibodies derived from COVID-19 donors that exhibited broad recognition and potent neutralization of zoonotic coronavirus and SARS-CoV-2 variants. C118-RBD and C022-RBD structures revealed CDRH3 mainchain H-bond interactions that extended an RBD β-sheet, thus reducing sensitivity to RBD sidechain changes, and epitopes that extended from the cryptic epitope to occlude ACE2 binding. A C118-spike trimer structure revealed rotated RBDs to allow cryptic epitope access 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.

Identifiers

PMID33948592
PMCPMC8095199
OpenAlexW3157272859

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.