Evidence map›Paper›PMID 41474620›Full record

ArticleCell reports2026

Affinity maturation and light-chain-mediated paratope diversification anticipates viral evolution.

John Dingus, Duck-Kyun Yoo, Sachin Kumar, Yajuan Wang, Md Golam Kibria, Shahab Saghaei, Zahra Allahyari, Jessica W Chen, Natalie M Caputo, Jason Hwang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

John DingusDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Duck-Kyun YooDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Sachin KumarDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Yajuan WangDivision of Molecular Medicine, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Md Golam KibriaDivision of Molecular Medicine, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Shahab SaghaeiDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Zahra AllahyariDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Jessica W ChenDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Natalie M CaputoDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Jason HwangDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Bing ChenDivision of Molecular Medicine, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Duane R WesemannDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT, and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: dwesemann@bwh.harvard.edu.

Funding

Technology and Computational CoreP01AI165072 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI WESEMANN, DUANE R. · 2021 to 2023
$19.6M
MECHANISMS OF ARTHRITIC &DERMATOLOGY DISORDERST32AR007530 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Michael B. Brenner, Ellen M Gravallese · 1986 to 2026
$10.4M
Antibody Durability DynamicsR01AI170715 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Duane R. Wesemann · 2022 to 2026
$3.4M
Structural and functional integrity of antigen receptorsF31AI186232 · NIAID · HARVARD MEDICAL SCHOOL · PI Jessica WT Chen · 2024 to 2026
$119k
NIAID NIH HHS F31 AI186232NIAID NIH HHS P01 AI165072NIAID NIH HHS R01 AI170715NIAMS NIH HHS T32 AR007530
6 · The paper itself

Abstract

A key goal of vaccinology is to train the immune system to combat current pathogens while preparing it for future variants. Here, we investigate how Wuhan strain severe acute respiratory syndrome coronavirus 2 mRNA vaccination generates "anticipatory breadth" in an antibody family exhibiting germline complementarity to the ACE2 binding site on the receptor-binding-domain (RBD). IGHV3-53/66 antibodies from infection-naive vaccinees frequently neutralize Omicron variants and contain hallmark breadth-enhancing mutations. While Omicron breakthrough infection does not alter IGHV3-53/66 mutation frequencies, it modifies Ig light-chain pairing frequencies, suggesting variant-driven selection for favorable pairings. Structural analyses of IGHV3-53/66-RBD complexes show that hallmark heavy-chain mutations refine interactions with conserved RBD residues, while alternative Ig light-chain pairings modify contacts at Omicron mutation sites. Together, these findings support a cooperative model of anticipatory breadth involving targeting of a functionally constrained epitope, affinity maturation to establish an affinity buffer, and alternative Ig light-chain pairings to diversify paratopes-providing a mechanistic framework for anticipating viral evolution.

Indexed as

Antibody AffinityCOVID-19Immunoglobulin Light ChainsSARS-CoV-2Angiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralEpitopesEvolution, MolecularHumansMutationSpike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralEpitopesImmunoglobulin Light ChainsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2antibodyanticipatory breadthCP: immunologygermlineIGHV3-53immune escapeneutralization breadthSARS-CoV-2SHMsomatic hypermutationvaccine

Identifiers

PMID41474620
PMCPMC12952975

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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.