Evidence map›Paper›PMID 34648356›Full record

ArticleScience immunology2021

Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses.

Jared Feldman, Julia Bals, Clara G Altomare, Kerri St Denis, Evan C Lam, Blake M Hauser, Larance Ronsard, Maya Sangesland, Thalia Bracamonte Moreno, Vintus Okonkwo and 5 more

Open access · greenAbstract read
In one paragraph

Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025
    Article
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  14. Monoclonal Antibody Generation Using Single B Cell Screening for Treating Infectious Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  15. Review
  16. Article
  17. Article
  18. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Jared FeldmanRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-4387-9954
Julia BalsRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-9740-7637
Clara G AltomareDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-7564-704X
Kerri St DenisRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-6324-7890
Evan C LamRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-5556-2559
Blake M HauserRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-0100-1684
Larance RonsardRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-5307-1940
Maya SangeslandRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Thalia Bracamonte MorenoRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Vintus OkonkwoRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Nathania HartojoRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-6340-9087
Alejandro B BalazsRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-1767-3944
Goran BajicDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-0480-4324
Daniel LingwoodRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0001-5631-9238
Aaron G SchmidtRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0003-3627-2553
Ragon Institute of MGH, MIT and Harvard · USIcahn School of Medicine at Mount Sinai · USHarvard University · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
NCCAT: National Center for CryoEM Access and Training- Supplement for Windows 10 and FFIU24GM129539 · NIGMS · NEW YORK STRUCTURAL BIOLOGY CENTER · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2018 to 2023
$53.9M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
TRAINING PROGRAM: MECHANISMS OF VIRUS-HOST INTERACTIONST32AI007647 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI Domenico Tortorella · 2000 to 2026
$11.5M
MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
Epitope focusing to the receptor binding motif for a universal coronavirus vaccineR01AI146779 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SCHMIDT, AARON GREGORY · 2019 to 2023
$4.2M
Innate-like BCR activity as a template for universal vaccination against influenza virusR01AI137057 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI CHACKERIAN, BRYCE C, LINGWOOD, DANIEL · 2018 to 2022
$2.6M
Engineering Humoral Immunity to Functionally Cure HIV InfectionDP2DA040254 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI BALAZS, ALEJANDRO BENJAMIN · 2015 to 2015
$2.6M
Defining and Exploiting a Genetic Template for an HIV VaccineDP2DA042422 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI LINGWOOD, DANIEL · 2016 to 2016
$2.6M
Triggering germline-encoded broadly neutralizing antibody responses against influenza virusR01AI153098 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI BATISTA, FACUNDO DAMIAN, LINGWOOD, DANIEL · 2020 to 2023
$2.1M
CDRH3-independent B cell stimulation to selectively expand VRC01 lineages from a fully humanized immunoglobulin repertoireR01AI124378 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI CHACKERIAN, BRYCE C, LINGWOOD, DANIEL · 2017 to 2020
$2.0M
Systemic coordination of pro-inflammatory immune reactions through dendritic cell-restricted sIL6R biogenesisR01AI155447 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LINGWOOD, DANIEL · 2021 to 2025
$2.0M
NIAID NIH HHS F30 AI160908NIAID NIH HHS R01 AI124378NIAID NIH HHS R01 AI137057NIAID NIH HHS R01 AI146779NIAID NIH HHS R01 AI153098NIAID NIH HHS R01 AI155447NIAID NIH HHS T32 AI007245NIAID NIH HHS T32 AI007647NIAID NIH HHS U19 AI057229NIDA NIH HHS DP2 DA040254NIDA NIH HHS DP2 DA042422NIGMS NIH HHS T32 GM007753NIGMS NIH HHS U24 GM129539
6 · The paper itself

Abstract

Initial exposure to a pathogen elicits an adaptive immune response to control and eradicate the threat. Interrogating the abundance and specificity of the naive B cell repertoire drives understanding of how to mount protective responses. Here, we isolated naive B cells from eight seronegative human donors targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD). Single-cell B cell receptor (BCR) sequencing identified diverse gene usage and no restriction on complementarity determining region length. A subset of recombinant antibodies produced by naive B cell precursors bound to SARS-CoV-2 RBD and engaged circulating variants including B.1.1.7, B.1.351, and B.1.617.2, as well as preemergent bat-derived coronaviruses RaTG13, SHC104, and WIV1. By structural characterization of a naive antibody in complex with SARS-CoV-2 spike, we identified a conserved mode of recognition shared with infection-induced antibodies. We found that representative naive antibodies could signal in a B cell activation assay, and by using directed evolution, we could select for a higher-affinity RBD interaction, conferred by a single amino acid change. The minimally mutated, affinity-matured antibodies also potently neutralized SARS-CoV-2. Understanding the SARS-CoV-2 RBD–specific naive repertoire may inform potential responses capable of recognizing future SARS-CoV-2 variants or emerging coronaviruses, enabling the development of pan-coronavirus vaccines aimed at engaging protective germline responses.

Indexed as

Antibodies, NeutralizingAntigens, ViralB-LymphocytesCoronavirusCOVID-19COVID-19 VaccinesEpitopesHumansLymphocyte ActivationSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, NeutralizingAntigens, ViralCOVID-19 VaccinesEpitopesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID34648356
PMCPMC8720485
OpenAlexW3205383079

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.