Evidence map›Paper›PMID 40803328›Full record

ArticleCell reports2025

Clonotype-enriched somatic hypermutations drive affinity maturation of a public human antibody targeting an occluded sarbecovirus epitope.

Vishal N Rao, Iden A Sapse, Hallie Cohn, Duck-Kyun Yoo, Pei Tong, Jordan J Clark, Bailey Bozarth, Yuexing Chen, Komal Srivastava, Gagandeep Singh and 5 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
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  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Vishal N RaoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Iden A SapseDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Hallie CohnDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Duck-Kyun YooDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA.
Pei TongDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA.
Jordan J ClarkDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bailey BozarthDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Yuexing ChenDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Komal SrivastavaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Gagandeep SinghDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Florian KrammerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria.
Viviana SimonDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Duane R WesemannDepartment of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA. Electronic address: dwesemann@bwh.harvard.edu.
Goran BajicDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: goran.bajic@mssm.edu.
Camila H CoelhoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: camila.coelho@mssm.edu.

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
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
Conduits: Mount Sinai Health System Translational Science HubUL1TR004419 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Rosalind J Wright · 2022 to 2026
$46.4M
Technology and Computational CoreP01AI165072 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI SAPHIRE, ERICA OLLMANN · 2021 to 2023
$19.6M
NIH FIRST Cohort Cluster Hiring Initiative at Icahn School of Medicine at Mount SinaiU54CA267776 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Nihal Mohamed · 2021 to 2026
$17.4M
Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)U19AI168631 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ana Fernandez-Sesma · 2022 to 2026
$14.4M
Understanding antibody responses and defining correlates of protection for endemic and pandemic coronavirus strainsP01AI172531 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Florian Krammer · 2023 to 2026
$12.5M
Structural interrogation of vaccine- and infection-induced B cell responsesR01AI168178 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Goran Bajic · 2022 to 2026
$3.9M
Antibody Durability DynamicsR01AI170715 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Duane R. Wesemann · 2022 to 2026
$3.4M
UC San Diego RAPID Faculty Development Program in Infectious DiseasesR25AI147376 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADRIANA H TREMOULET, Joann Trejo · 2020 to 2026
$2.5M
Strengthening the ISMMS research and response capabilities for pathogens of pandemic potentialG20AI174733 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ALBRECHT, RANDY A. · 2022 to 2022
$2.3M
COVID and Translational Science supercomputer (CATS)S10OD030463 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2021 to 2021
$2.0M
NCATS NIH HHS UL1 TR004419NCI NIH HHS P30 CA016087NCI NIH HHS U54 CA267776NIAID NIH HHS F31 AI194512NIAID NIH HHS G20 AI174733NIAID NIH HHS P01 AI165072NIAID NIH HHS P01 AI172531NIAID NIH HHS R01 AI168178NIAID NIH HHS R01 AI170715NIAID NIH HHS R25 AI147376NIAID NIH HHS U19 AI168631NIGMS NIH HHS U24 GM129539NIH HHS S10 OD026880NIH HHS S10 OD030463
6 · The paper itself

Abstract

Investigating public antibodies that recognize conserved epitopes is critical for vaccine development. Identifying somatic hypermutations (SHMs) that enhance antigen affinity in these public antibodies is key to guiding vaccine design for better protection against pathogens. We propose that affinity-enhancing SHMs are selectively enriched in public antibody clonotypes, surpassing the background frequency seen in antibodies carrying the same V genes but with different epitope specificities. Using M15, a human IGHV4-59/IGKV3-20 public antibody as a model, we compare SHM signatures in antibodies that use the same V genes but recognize other epitopes. We identified clonotype-enriched mutations in the light chain of M15 and showed that, in combination, these SHMs enhance binding to a previously uncharacterized Sarbecovirus epitope, with antibody responses to it increasing after sequential vaccination. Our findings identify convergence and clonotype enrichment as features of affinity-enhancing SHMs in public antibodies, which can help guide vaccine design aimed at eliciting such antibodies.

Indexed as

Antibodies, ViralAntibody AffinityEpitopesSomatic Hypermutation, ImmunoglobulinHumansAntibodies, ViralEpitopesaffinity maturationantibody clonotypecentral interface epitopeCP: Immunologycryo-EMprotein structurepublic antibodiesSarbecovirusessomatic hypermutation

Identifiers

PMID40803328
PMCPMC12477886

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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.