Evidence map›Paper›PMID 23460696›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies.

Audray K Harris, Joel R Meyerson, Yumiko Matsuoka, Oleg Kuybeda, Amy Moran, Donald Bliss, Suman R Das, Jonathan W Yewdell, Guillermo Sapiro, Kanta Subbarao and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
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

81 citing papers in PubMed, 115 citations in OpenAlex.

  1. Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Trial
  2. Article
  3. Article
  4. DNA Nanostructure-Templated Multivalency Enables Broad-Spectrum Virus Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  7. Review
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  15. γδ T cell antigen receptor polyspecificity enables T cell responses to a broad range of immune challenges.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Article
  17. Article
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  19. Review
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21 more citing papers are in PubMed but not listed here.

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

11 authors at 7 institutions in 3 countries.

Audray K HarrisLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Joel R Meyerson
Yumiko Matsuoka
Oleg Kuybeda
Amy Moran
Donald Bliss
Suman R Das
Jonathan W Yewdell
Guillermo Sapiro
Kanta Subbarao
Sriram Subramaniam
National Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USOffice of Infectious Diseases · USUniversity of Minnesota · USCancer Institute (WIA) · INCenter for Cancer Research · USMRC Mitochondrial Biology Unit · GB

Funding

Structural Biology of Influenza EpitopesZIAAI001180 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HARRIS, AUDRAY · 2013 to 2025
$12.7M
Technology Development for 3D Electron MicroscopyZIABC010826 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SUBRAMANIAM, SRIRAM · 2009 to 2019
$9.1M
Molecular structures of membrane protein assembliesZIABC010824 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SUBRAMANIAM, SRIRAM · 2009 to 2019
$8.0M
HIV neutralization and mechanisms of cellular entryZIABC010825 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SUBRAMANIAM, SRIRAM · 2009 to 2019
$8.0M
Biology, Evolution and Pathogenesis of Influenza A VirusZIAAI001014 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BENNINK, JACK R · 2009 to 2020
$5.6M
Preclinical Studies of Vaccines for Pandemic H1N1 InfluenzaZIAAI001109 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SUBBARAO, KANTA · 2009 to 2017
$5.3M
Antigenic Drift in Influenza A VirusZIAAI001055 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI YEWDELL, JONATHAN W · 2009 to 2015
$3.1M
Intramural NIH HHS
6 · The paper itself

Abstract

Rapid antigenic variation of HA, the major virion surface protein of influenza A virus, remains the principal challenge to the development of broader and more effective vaccines. Some regions of HA, such as the stem region proximal to the viral membrane, are nevertheless highly conserved across strains and among most subtypes. A fundamental question in vaccine design is the extent to which HA stem regions on the surface of the virus are accessible to broadly neutralizing antibodies. Here we report 3D structures derived from cryoelectron tomography of HA on intact 2009 H1N1 pandemic virions in the presence and absence of the antibody C179, which neutralizes viruses expressing a broad range of HA subtypes, including H1, H2, H5, H6, and H9. By fitting previously derived crystallographic structures of trimeric HA into the density maps, we deduced the locations of the molecular surfaces of HA involved in interaction with C179. Using computational methods to distinguish individual unliganded HA trimers from those that have bound C179 antibody, we demonstrate that ∼75% of HA trimers on the surface of the virus have C179 bound to the stem domain. Thus, despite their close packing on the viral membrane, the majority of HA trimers on intact virions are available to bind anti-stem antibodies that target conserved HA epitopes, establishing the feasibility of universal influenza vaccines that elicit such antibodies.

Indexed as

Models, MolecularProtein MultimerizationAntibodies, NeutralizingAntibodies, ViralAntibody SpecificityHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A Virus, H1N1 SubtypeInfluenza, HumanPandemicsProtein Structure, QuaternaryAntibodies, NeutralizingAntibodies, ViralH1N1 virus hemagglutininHemagglutinin Glycoproteins, Influenza Virus

Identifiers

PMID23460696
PMCPMC3607006
OpenAlexW2049788122

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.