Evidence map›Paper›PMID 40816277›Full record

ArticleStructure (London, England : 1993)2025

The N terminus of H3-influenza hemagglutinin as a site-of-vulnerability to neutralizing antibody.

Reda Rawi, Nicholas C Morano, Crystal Sao-Fong Cheung, Haijuan Du, Jason Gorman, Madhu Prabhakaran, Jordan E Becker, Tatsiana Bylund, Sam Charaf, Xuejun Chen and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Egyptian rousette bat humoral immunity to H9 influenza hemagglutinin.bioRxiv : the preprint server for biology · 2026
    Article
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

22 authors.

Reda RawiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: reda.rawi@nih.gov.
Nicholas C MoranoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Crystal Sao-Fong CheungVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Haijuan DuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Jason GormanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Madhu PrabhakaranVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Jordan E BeckerAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Tatsiana BylundVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Sam CharafVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Xuejun ChenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Myungjin LeeVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Darcy R HarrisVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Adam S OliaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Li OuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lingshu WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Shuishu WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Masaru KanekiyoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Adrian B McDermottVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lawrence ShapiroVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: pdk3@cumc.columbia.edu.

Funding

TRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7M
Rational Immunogen Design Using Computational MethodsZICAI005114 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.3M
Gates Foundation INV-029369Intramural NIH HHS ZIC AI005114NIGMS NIH HHS P41 GM103310
6 · The paper itself

Abstract

The N terminus of the H3 subtype of influenza virus hemagglutinin is ∼10 residues longer than the N termini of most other hemagglutinins. As conserved, exposed, and linear regions may be good vaccine targets, we investigated the vaccine utility of the extended H3-N terminus. First, we identified antibody 5E10, for which structure and binding analyses revealed recognition of the H3-N terminus. Second, we immunized mice with immunogens incorporating the H3-N terminus, boosted with hemagglutinin trimer, and isolated antibodies from immunogen-elicited B cells that bound both H3-N terminus and hemagglutinin trimer. However, hemagglutinin-complex structures of two such antibodies, 3864-6 and 3864-10, that neutralized H3-influenza strains, revealed only peripheral recognition of the hemagglutinin N terminus. Collectively, these results reveal the N terminus of H3 hemagglutinin to be a suboptimal vaccine target and suggest that-in addition to being conserved, flexible, and accessible-other factors influence the elicitation of potent broadly neutralizing responses.

Indexed as

Antibodies, NeutralizingAntibodies, ViralHemagglutinin Glycoproteins, Influenza VirusAnimalsEpitopesFemaleHumansInfluenza VaccinesMiceMice, Inbred BALB CModels, MolecularProtein BindingAntibodies, NeutralizingAntibodies, ViralEpitopesHemagglutinin Glycoproteins, Influenza VirusInfluenza Vaccinescryo-EMimmune focusinginfluenza H3 N terminuspeptide immunizationprime-booststructure-based vaccine design

Identifiers

PMID40816277
PMCPMC12416542

What OpenQuestion holds

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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.