Evidence map›Paper›PMID 40815640›Full record

ArticleScience advances2025

Functional and epitope specific monoclonal antibody discovery directly from immune sera using cryo-EM.

James A Ferguson, Sai Sundar Rajan Raghavan, Garazi Peña Alzua, Disha Bhavsar, Jiachen Huang, Alesandra J Rodriguez, Jonathan L Torres, Maria Bottermann, Julianna Han, Florian Krammer and 2 more

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

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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

12 authors.

James A FergusonDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-2891-0850
Sai Sundar Rajan RaghavanDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-2575-2685
Garazi Peña AlzuaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-9139-9915
Disha BhavsarDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-1564-3298
Jiachen HuangDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-7624-7390
Alesandra J RodriguezDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jonathan L TorresDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-0137-8497
Maria BottermannThe Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-8178-100X
Julianna HanDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-3402-2609
Florian KrammerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-4121-776X
Facundo D BatistaThe Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-1130-9463
Andrew B WardDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-7153-3769

Funding

NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00014 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GARCIA-SASTRE, ADOLFO · 2021 to 2025
$62.6M
Dissecting Polyclonal Sera to Reveal Correlates of Productive Immune Responses to HIVR01AI136621 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Lars Oliver Hangartner, Andrew Barrett Ward · 2018 to 2026
$8.0M
NIAID NIH HHS R01 AI136621NIH HHS 75N93021C00014
6 · The paper itself

Abstract

Antibodies are crucial therapeutics, comprising a substantial portion of approved drugs due to their safety and clinical efficacy. Traditional antibody discovery methods are labor-intensive, limiting scalability and high-throughput analysis. Here, we improved upon our streamlined approach combining structural analysis and bioinformatics to infer heavy and light chain sequences from cryo-EM (cryo-electron microscopy) maps of serum-derived polyclonal antibodies (pAbs) bound to antigens. Using ModelAngelo, an automated structure-building tool, we accelerated pAb sequence determination and identified sequence matches in B cell repertoires via ModelAngelo-derived hidden Markov models (HMMs) associated with pAb structures. Benchmarking against results from a nonhuman primate HIV vaccine trial, our pipeline reduced analysis time from weeks to under a day with higher precision. Validation with murine immune sera from influenza vaccination revealed multiple protective antibodies. This workflow enhances antibody discovery, enabling faster, more accurate mapping of polyclonal responses with broad applications in vaccine development and therapeutic antibody discovery.

Indexed as

Antibodies, MonoclonalCryoelectron MicroscopyEpitopesAnimalsHumansInfluenza VaccinesMiceAntibodies, MonoclonalEpitopesInfluenza Vaccines

Identifiers

PMID40815640
PMCPMC12356236

What OpenQuestion holds

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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.