Evidence map›Paper›PMID 26098893›Full record

ArticlePloS one2015

A Cysteine Zipper Stabilizes a Pre-Fusion F Glycoprotein Vaccine for Respiratory Syncytial Virus.

Guillaume B E Stewart-Jones, Paul V Thomas, Man Chen, Aliaksandr Druz, M Gordon Joyce, Wing-Pui Kong, Mallika Sastry, Cinque Soto, Yongping Yang, Baoshan Zhang and 10 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Review
  3. Immunofocusing design of a fusion glycoprotein monomer vaccine for respiratory syncytial virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. The Versatile Manipulations of Self-Assembled Proteins in Vaccine Design.International journal of molecular sciences · 2021
    Review
  17. Vaccines for COVID-19.Clinical and experimental immunology · 2020
    Review
  18. Article
  19. Article
  20. 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

20 authors at 4 institutions in 1 country.

Guillaume B E Stewart-JonesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Paul V ThomasVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Man ChenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Aliaksandr DruzVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
M Gordon JoyceVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Wing-Pui KongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Mallika SastryVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Cinque SotoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Yongping YangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Lei ChenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Gwo-Yu ChuangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Ivelin S GeorgievVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Jason S McLellanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Sanjay SrivatsanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Ulrich BaxaElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Barney S GrahamVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
National Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USDartmouth College · USLeidos (United States) · US

Funding

Design Of ImmunogensZIAAI005024 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$21.5M
Rational Immunogen Design Using Computational MethodsZICAI005114 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.3M
Computational Tools for Structural AnalysisZICAI005112 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.1M
Computational Algorithms, Methods, and Tools for Structure-Based Vaccine DesignZICAI005113 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KWONG, PETER D · 2010 to 2019
$2.5M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA AI005024NCI NIH HHS HHSN261200800001ENIAID NIH HHS ZIA AI005024-13
6 · The paper itself

Abstract

Recombinant subunit vaccines should contain minimal non-pathogen motifs to reduce potential off-target reactivity. We recently developed a vaccine antigen against respiratory syncytial virus (RSV), which comprised the fusion (F) glycoprotein stabilized in its pre-fusion trimeric conformation by "DS-Cav1" mutations and by an appended C-terminal trimerization motif or "foldon" from T4-bacteriophage fibritin. Here we investigate the creation of a cysteine zipper to allow for the removal of the phage foldon, while maintaining the immunogenicity of the parent DS-Cav1+foldon antigen. Constructs without foldon yielded RSV F monomers, and enzymatic removal of the phage foldon from pre-fusion F trimers resulted in their dissociation into monomers. Because the native C terminus of the pre-fusion RSV F ectodomain encompasses a viral trimeric coiled-coil, we explored whether introduction of cysteine residues capable of forming inter-protomer disulfides might allow for stable trimers. Structural modeling indicated the introduced cysteines to form disulfide "rings", with each ring comprising a different set of inward facing residues of the coiled-coil. Three sets of rings could be placed within the native RSV F coiled-coil, and additional rings could be added by duplicating portions of the coiled-coil. High levels of neutralizing activity in mice, equivalent to that of the parent DS-Cav1+foldon antigen, were elicited by a 4-ring stabilized RSV F trimer with no foldon. Structure-based alteration of a viral coiled-coil to create a cysteine zipper thus allows a phage trimerization motif to be removed from a candidate vaccine antigen.

Indexed as

AnimalsAntibodies, NeutralizingAntigens, ViralBacteriophage T4Caveolin 1Cell LineCysteineImmunizationMiceMice, Inbred BALB CMice, Inbred C57BLRespiratory Syncytial VirusesRespiratory Syncytial Virus VaccinesVaccines, SubunitViral Fusion ProteinsViral ProteinsAntibodies, NeutralizingAntigens, ViralCav1 protein, mouseCaveolin 1Cysteinefibritin protein, Enterobacteria phage T4Respiratory Syncytial Virus VaccinesVaccines, SubunitViral Fusion ProteinsViral Proteins

Identifiers

PMID26098893
PMCPMC4476739
OpenAlexW1508193774

What OpenQuestion holds

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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.