Evidence map›Paper›PMID 28404847›Full record

ArticleJournal of virology2017

Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation.

Normand Blais, Martin Gagné, Yoshitomo Hamuro, Patrick Rheault, Martine Boyer, Ann-Muriel Steff, Guy Baudoux, Vincent Dewar, Josée Demers, Jean-Louis Ruelle and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Interpretation of Hydrogen/Deuterium Exchange Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024
    Article
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  8. Review
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  17. Review
  18. A multifaceted approach to RSV vaccination.Human vaccines & immunotherapeutics · 2018
    Review
  19. 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

11 authors at 1 institution in 1 country.

Normand BlaisGSK Vaccines, Laval, Canada normand.x.blais@gsk.com.
Martin GagnéGSK Vaccines, Laval, Canada.
Yoshitomo HamuroExSAR Corporation, Monmouth Junction, New Jersey, USA.
Patrick RheaultGSK Vaccines, Laval, Canada.
Martine BoyerGSK Vaccines, Laval, Canada.
Ann-Muriel SteffGSK Vaccines, Laval, Canada.
Guy BaudouxGSK Vaccines, Rixensart, Belgium.
Vincent DewarGSK Vaccines, Rixensart, Belgium.
Josée DemersGSK Vaccines, Laval, Canada.
Jean-Louis RuelleGSK Vaccines, Rixensart, Belgium.
Denis MartinGSK Vaccines, Laval, Canada.
GlaxoSmithKline (Belgium) · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralHumansMacromolecular SubstancesMass SpectrometryMicroscopy, ElectronModels, MolecularProtein BindingProtein FoldingProtein MultimerizationProtein StabilityRecombinant ProteinsViral Fusion ProteinsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralF protein, human respiratory syncytial virusMacromolecular SubstancesRecombinant ProteinsViral Fusion Proteinshydrogen/deuterium exchange mass spectrometrypre-F conformationrespiratory syncytial virus F proteinvaccine antigen

Identifiers

PMID28404847
PMCPMC5469252
OpenAlexW2606445530

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.