Evidence map›Paper›PMID 25404330›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Relating influenza virus membrane fusion kinetics to stoichiometry of neutralizing antibodies at the single-particle level.

Jason J Otterstrom, Boerries Brandenburg, Martin H Koldijk, Jarek Juraszek, Chan Tang, Samaneh Mashaghi, Ted Kwaks, Jaap Goudsmit, Ronald Vogels, Robert H E Friesen 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, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

42 citing papers in PubMed, 67 citations in OpenAlex.

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  6. Virion-associated influenza hemagglutinin clusters upon sialic acid binding visualized by cryoelectron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  11. The Art of Viral Membrane Fusion and Penetration.Sub-cellular biochemistry · 2023
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  15. Engineering recombinantly expressed lectin-based antiviral agents.Frontiers in cellular and infection microbiology · 2022
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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

11 authors at 3 institutions in 3 countries.

Jason J OtterstromHarvard University Biophysics Program, Harvard Medical School, Boston, MA 02115; Centre for Synthetic Biology, Zernike Institute for Advanced Materials, University of Groningen, 9747 AG, Groningen, The Netherlands; and.ORCID http://orcid.org/0000-0002-0176-9976
Boerries BrandenburgCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Martin H KoldijkCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Jarek JuraszekCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Chan TangCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Samaneh MashaghiCentre for Synthetic Biology, Zernike Institute for Advanced Materials, University of Groningen, 9747 AG, Groningen, The Netherlands; and.
Ted KwaksCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Jaap GoudsmitCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Ronald VogelsCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Robert H E FriesenCrucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.
Antoine M van OijenCentre for Synthetic Biology, Zernike Institute for Advanced Materials, University of Groningen, 9747 AG, Groningen, The Netherlands; and a.m.van.oijen@rug.nl.
Janssen (Belgium) · BEUniversity of Groningen · NLHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ability of antibodies binding the influenza hemagglutinin (HA) protein to neutralize viral infectivity is of key importance in the design of next-generation vaccines and for prophylactic and therapeutic use. The two antibodies CR6261 and CR8020 have recently been shown to efficiently neutralize influenza A infection by binding to and inhibiting the influenza A HA protein that is responsible for membrane fusion in the early steps of viral infection. Here, we use single-particle fluorescence microscopy to correlate the number of antibodies or antibody fragments (Fab) bound to an individual virion with the capacity of the same virus particle to undergo membrane fusion. To this end, individual, infectious virus particles bound by fluorescently labeled antibodies/Fab are visualized as they fuse to a planar, supported lipid bilayer. The fluorescence intensity arising from the virus-bound antibodies/Fab is used to determine the number of molecules attached to viral HA while a fluorescent marker in the viral membrane is used to simultaneously obtain kinetic information on the fusion process. We experimentally determine that the stoichiometry required for fusion inhibition by both antibody and Fab leaves large numbers of unbound HA epitopes on the viral surface. Kinetic measurements of the fusion process reveal that those few particles capable of fusion at high antibody/Fab coverage display significantly slower hemifusion kinetics. Overall, our results support a membrane fusion mechanism requiring the stochastic, coordinated action of multiple HA trimers and a model of fusion inhibition by stem-binding antibodies through disruption of this coordinated action.

Indexed as

Antibodies, NeutralizingHemagglutinin Glycoproteins, Influenza VirusHost-Pathogen InteractionsHumansImmunoglobulin Fab FragmentsInfluenza A virusInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza, HumanKineticsMembrane FusionMicroscopy, Electron, TransmissionMicroscopy, FluorescenceMonte Carlo MethodProtein BindingVirionAntibodies, NeutralizingHemagglutinin Glycoproteins, Influenza VirusImmunoglobulin Fab Fragmentshemagglutinininfluenzamembrane fusionneutralization stoichiometryneutralizing antibody

Identifiers

PMID25404330
PMCPMC4260548
OpenAlexW2082026765

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.