Evidence map›Paper›PMID 21994355›Full record

ArticleClinical and vaccine immunology : CVI2011

Generation and characterization of a live attenuated enterotoxigenic Escherichia coli combination vaccine expressing six colonization factors and heat-labile toxin subunit B.

Arthur K Turner, Jonathan C Stephens, Juliet C Beavis, Judith Greenwood, Cornelia Gewert, Roger Randall, Donna Freeman, Michael J Darsley

Open access · diamondAbstract read
In one paragraph

Article in Clinical and vaccine immunology : CVI, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Trial
  2. Review
  3. Recent progress in enterotoxigenicInfection and immunity · 2025
    Review
  4. The Diversity ofMicroorganisms · 2023
    Review
  5. Review
  6. Article
  7. Confronting challenges to enterotoxigenicFrontiers in tropical diseases · 2021
    Article
  8. Review
  9. Article
  10. A roadmap for enterotoxigenicHuman vaccines & immunotherapeutics · 2019
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. [Acute diarrheal disease caused by enteropathogenic Escherichia coli in Colombia].Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia · 2014
    Review
  18. Review
  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

8 authors.

Arthur K TurnerTD Vaccines A/S, Aspvej 12, Rauf, Skørping 9520, Denmark.
Jonathan C Stephens
Juliet C Beavis
Judith Greenwood
Cornelia Gewert
Roger Randall
Donna Freeman
Michael J Darsley

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Live attenuated oral enterotoxigenic Escherichia coli (ETEC) vaccines have been demonstrated to be safe and immunogenic in human volunteers and to provide a viable approach to provide protection against this important pathogen. This report describes the construction of new ETEC vaccine candidate strains from recent clinical isolates and their characterization. All known genes for ETEC toxins were removed, and attenuating deletion mutations were made in the aroC, ompC, and ompF chromosomal genes. An isolate expressing coli surface antigen 2 (CS2), CS3, heat-labile toxin (LT), heat-stable toxin (ST), and enteroaggregative Escherichia coli heat-stable toxin 1 (EAST1) was attenuated to generate ACAM2007. The subsequent insertion of the operon encoding CS1 created ACAM2017, and this was further modified by the addition of an expression cassette containing the eltB gene, encoding a pentamer of B subunits of LT (LTB), to generate ACAM2027. Another isolate expressing CS5, CS6, LT, ST, and EAST1 was attenuated to generate ACAM2006, from which a lysogenic prophage was deleted to create ACAM2012 and an LTB gene was introduced to form ACAM2022. Finally, a previously described vaccine strain, ACAM2010, had the eltB gene incorporated to generate ACAM2025. All recombinant genes were incorporated into the chromosomal sites of the attenuating mutations to ensure maximal genetic stability. The expression of the recombinant antigens and the changes in plasmids accompanying the deletion of toxin genes are described. Strains ACAM2025, ACAM2022, and ACAM2027 have been combined to create the ETEC vaccine formulation ACE527, which has recently successfully completed a randomized, double-blind, placebo-controlled phase I trial and is currently undergoing a randomized, double-blind placebo-controlled phase II challenge trial, both in healthy adult volunteers.

Indexed as

Bacterial ToxinsEnterotoxigenic Escherichia coliEscherichia coli VaccinesHumansPlasmidsRandomized Controlled Trials as TopicVaccines, AttenuatedVaccines, CombinedVaccines, SyntheticVirulence FactorsBacterial ToxinsEscherichia coli VaccinesVaccines, AttenuatedVaccines, CombinedVaccines, SyntheticVirulence Factors

Identifiers

PMID21994355
PMCPMC3232708
OpenAlexW2046397739

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.