Evidence map›Paper›PMID 34015271›Full record

ArticleCell2021

B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV.

Johannes F Scheid, Christopher O Barnes, Basak Eraslan, Andrew Hudak, Jennifer R Keeffe, Lisa A Cosimi, Eric M Brown, Frauke Muecksch, Yiska Weisblum, Shuting Zhang and 26 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
5.7field-weighted citation impact, top 3% of its field
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

75 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
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  7. Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  18. B cell tolerance and autoimmunity: Lessons from repertoires.The Journal of experimental medicine · 2024
    Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors at 7 institutions in 1 country.

Johannes F ScheidBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Christopher O BarnesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Basak EraslanBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Andrew HudakBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Jennifer R KeeffeDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Lisa A CosimiDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Eric M BrownBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Frauke MueckschLaboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA.
Yiska WeisblumLaboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA.
Shuting ZhangBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Toni DeloreyBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ann E WoolleyDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Fadi GhantousCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Sung-Moo ParkBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Devan PhillipsBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Betsabeh TusiBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Kathryn E Huey-TubmanDivision 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.
Kara RzasaBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Theodora HatziioannoLaboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA.
Michael A DurneyBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Xiebin GuBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Takuya TadaDepartment of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Nathaniel R LandauDepartment of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Anthony P WestDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Orit Rozenblatt-RosenBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Lindsey R BadenDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Daniel B GrahamBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jacques DeguineBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Paul D BieniaszLaboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Deborah HungBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: bjorkman@caltech.edu.
Ramnik J XavierBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
Broad Institute · USCalifornia Institute of Technology · USBrigham and Women's Hospital · USRockefeller University · USBeth Israel Deaconess Medical Center · USNew York University · USHoward Hughes Medical Institute · US

Funding

Harvard Medical School Vaccine Clinical Trials UnitUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Lindsey Robert Baden, Daniel R. Kuritzkes · 2012 to 2026
$57.2M
RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteinsU19AI142784 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI CRAVATT, BENJAMIN F · 2019 to 2023
$36.9M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Virus TransmissionP50AI150464 · NIAID · UNIVERSITY OF UTAH · PI HOPE, THOMAS · 2019 to 2021
$14.9M
Systematic dissection of gut cellular circuits [at single cell resolution]RC2DK114784 · NIDDK · BROAD INSTITUTE, INC. · PI ASHENBERG, ORR, GRAHAM, DANIEL BARTHOLOMEW · 2017 to 2021
$9.0M
Virology CoreP01AI138938 · NIAID · ROCKEFELLER UNIVERSITY · PI BJORKMAN, PAMELA J · 2018 to 2022
$8.4M
Therapeutic Dendritic Cell Vaccine for HIVDP1DA046100 · NIDA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI LANDAU, NATHANIEL R. · 2018 to 2023
$4.2M
Dendritic Cell Vaccine for Controlling the Latent ReservoirR33AI122390 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KIEM, HANS-PETER, KITCHEN, SCOTT G · 2018 to 2020
$1.6M
Lentiviral Vector Vaccine for HIV-1K08AI120898 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI NORTON, THOMAS D · 2015 to 2018
$774k
Dendritic Cell Vaccine for Controlling the Latent ReservoirR21AI122390 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KIEM, HANS-PETER, KITCHEN, SCOTT G · 2016 to 2017
$457k
NIAID NIH HHS K08 AI120898NIAID NIH HHS P01 AI138938NIAID NIH HHS P50 AI150464NIAID NIH HHS R21 AI122390NIAID NIH HHS R33 AI122390NIAID NIH HHS U19 AI142784NIAID NIH HHS UM1 AI069412NIDA NIH HHS DP1 DA046100NIDDK NIH HHS P30 DK043351NIDDK NIH HHS RC2 DK114784
6 · The paper itself

Abstract

Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntigen-Antibody ComplexAntigen-Antibody ReactionsB-LymphocytesCOVID-19Cryoelectron MicroscopyCrystallography, X-RayGene Expression ProfilingHumansImmunoglobulin AImmunoglobulin Variable RegionProtein DomainsProtein MultimerizationProtein Structure, QuaternaryAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntigen-Antibody ComplexImmunoglobulin AImmunoglobulin Variable RegionSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2COVID-19cryo-electron microscopydisordered CDRH3memory B cellsmonoclonal antibodiesSARS-CoV cross-neutralizationsingle B cell genomics

Identifiers

PMID34015271
PMCPMC8064835
OpenAlexW3157716983

What OpenQuestion holds

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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.