Evidence map›Paper›PMID 40674170›Full record

ArticleThe Journal of experimental medicine2025

In vivo antibody diversification targeting a conserved coronavirus epitope.

Usha Nair, Ziqi Feng, Madhav Akauliya, Abigail G Esposito, Charles R Crain, Edward D Lamperti, Thavaleak Prum, John E Warner, Lisa Madungwe, Gordon A Dale and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2025. 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.

No citing paper in PubMed yet.

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

15 authors.

Usha Nair *The Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0000-0002-1927-6889
Ziqi Feng *Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-5046-9788
Madhav Akauliya *The Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0009-0009-0325-6080
Abigail G Esposito *The Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0009-0000-6647-504X
Charles R Crain *The Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0009-0002-3350-2501
Edward D LampertiThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0009-0004-9328-6411
Thavaleak PrumThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0009-0004-6973-5053
John E WarnerThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0009-0001-1043-1643
Lisa MadungweThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0009-0002-4166-7840
Gordon A DaleThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0000-0002-4995-6017
Julie BoucauThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0000-0001-6731-7238
Gaurav D GaihaThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0000-0001-6875-4472
Meng YuanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-9754-4503
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-6469-2419
Facundo D BatistaThe Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.ORCID 0000-0002-6317-293X

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4M
A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Aina E. Cohen, KEITH O HODGSON · 2020 to 2026
$43.3M
DOE Office of Biological and Environmental ResearchGates Foundation INV-004923Gates Foundation INV-009585Massachusetts Consortium on Pathogen ReadinessNIAID NIH HHS P30 AI060354NIGMS NIH HHS P30 GM133894NIGMS NIH HHS P30GM133894NIH HHS P30AI060354Ragon Institute of Mass General, MIT and Harvard
6 · The paper itself

Abstract

To explore the use of human B cell receptor (BCR) knock-in mice for broadening antibody responses, we diversified CR3022, a monoclonal antibody (mAb) originally identified in a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) convalescent patient. This mAb targets a conserved epitope on the coronavirus receptor-binding domain (RBD). We took advantage of high- and low-affinity CR3022 BCR knock-in mice and immunized them with SARS-CoV-2 Wuhan RBD trimers to expand the breadth of these antibodies toward this virus. The resulting antibodies retained the ability to neutralize SARS-CoV and exhibited enhanced affinity and neutralization against the SARS-CoV-2 WA1/2020 strain, as well as the Delta (B.1.617.2) and Omicron KP.3 variants. They also showed broadened reactivity to two bat coronaviruses: WIV1 and, to a lesser potency, BtKY72. Structural analysis revealed key mutations that enhanced binding and neutralization, highlighting the importance of epitope accessibility and variant-specific conformations in antibody diversification. These findings demonstrate that human BCR-expressing mouse models can generate effective antibodies with broad neutralizing activity against viral epitopes.

Indexed as

Antibodies, MonoclonalAntibodies, ViralEpitopesSARS-CoV-2AnimalsAntibodies, NeutralizingCOVID-19Gene Knock-In TechniquesHumansMiceReceptors, Antigen, B-CellSpike Glycoprotein, CoronavirusAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesReceptors, Antigen, B-CellSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID40674170
PMCPMC12279014

What OpenQuestion holds

Textmetadata
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.