Evidence map›Paper›PMID 22526674›Full record

ArticleInfection and immunity2012

The A subunit of Escherichia coli heat-labile enterotoxin functions as a mucosal adjuvant and promotes IgG2a, IgA, and Th17 responses to vaccine antigens.

Elizabeth B Norton, Louise B Lawson, Zaid Mahdi, Lucy C Freytag, John D Clements

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

51 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Current Progress and Challenges in the Study of Adjuvants for Oral Vaccines.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Pig vaccination strategies based on enterotoxigenic Escherichia coli toxins.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021
    Review
  18. Article
  19. Article
  20. Review
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

5 authors at 1 institution in 1 country.

Elizabeth B NortonDepartment of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Louise B Lawson
Zaid Mahdi
Lucy C Freytag
John D Clements
Tulane University · US

Funding

Nanocarriers for transcutaneous delivery of vaccinesR01EB006493 · NIBIB · TULANE UNIVERSITY OF LOUISIANA · PI CLEMENTS, JOHN D · 2006 to 2009
$2.0M
NIBIB NIH HHS EB006493-04NIBIB NIH HHS R01 EB006493
6 · The paper itself

Abstract

Enterotoxigenic Escherichia coli (ETEC) produces both heat-labile (LT) and heat-stable (ST) enterotoxins and is a major cause of diarrhea in infants in developing countries and in travelers to those regions. In addition to inducing fluid secretion, LT is a powerful mucosal adjuvant capable of promoting immune responses to coadministered antigens. In this study, we examined purified A subunit to further understand the toxicity and adjuvanticity of LT. Purified A subunit was enzymatically active but sensitive to proteolytic degradation and unable to bind gangliosides, and even in the presence of admixed B subunit, it displayed low cyclic AMP (cAMP) induction and no enterotoxicity. Thus, the AB5 structure plays a key role in protecting the A subunit from proteolytic degradation and in delivering the enzymatic signals required for secretion. In contrast, the A subunit alone was capable of activating dendritic cells and enhanced immune responses to multiple antigens following intranasal immunization; therefore, unlike toxicity, LT adjuvanticity is not dependent on the AB5 holotoxin structure or the presence of the B subunit. However, immune responses were maximal when signals were received from both subunits either in an AB5 structure or with A and B admixed. Furthermore, the quality of the immune response (i.e., IgG1/IgG2 balance and mucosal IgA and IL-17 secretion) was determined by the presence of an A subunit, revealing for the first time induction of Th17 responses with the A subunit alone. These results have important implications for understanding ETEC pathogenesis, unraveling immunologic responses induced by LT-based adjuvants, and developing new mucosal vaccines.

Indexed as

Adjuvants, ImmunologicAdministration, IntranasalAnimalsBacterial ToxinsDendritic CellsEnterotoxinsEscherichia coli ProteinsImmunoglobulin AImmunoglobulin GMiceMice, Inbred BALB CProtein SubunitsTh17 CellsVaccinesAdjuvants, ImmunologicBacterial ToxinsEnterotoxinsEscherichia coli Proteinsheat-labile enterotoxin, E coliImmunoglobulin AImmunoglobulin GProtein SubunitsVaccines

Identifiers

PMID22526674
PMCPMC3416479
OpenAlexW2164225397

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.