Evidence map›Paper›PMID 10722611›Full record

Trial reportInfection and immunity2000

Pilot study of phoP/phoQ-deleted Salmonella enterica serovar typhimurium expressing Helicobacter pylori urease in adult volunteers.

H Angelakopoulos, E L Hohmann

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in Infection and immunity, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
15.7field-weighted citation impact, top 1% 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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.

  1. Prevalence and distribution of non-typhoidalEpidemiology and infection · 2023
    Pooled it
  2. Trial
  3. Review
  4. Frontiers in immunology · 2026
    Review
  5. UnravelingVaccines · 2025
    Review
  6. Article
  7. Genetic engineering ofEcoSal Plus · 2024
    Review
  8. Emerging Strategies against Non-TyphoidalCurrent issues in molecular biology · 2024
    Review
  9. Pathogens (Basel, Switzerland) · 2024
    Review
  10. Antibiotic Resistance ofJournal of Korean medical science · 2024
    Review
  11. How Long Will It Take to Launch an EffectiveInfection and drug resistance · 2023
    Review
  12. Protective immunity enhancedFrontiers in immunology · 2022
    Article
  13. Review
  14. Glycoconjugate vaccines againstBiophysical reviews · 2021
    Review
  15. Overview of the Nontyphoidal and Paratyphoidal Salmonella Vaccine Pipeline: Current Status and Future Prospects.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Review
  16. Article
  17. Bacteria-cancer interactions: bacteria-based cancer therapy.Experimental & molecular medicine · 2019
    Review
  18. AttenuatedVirulence · 2019
    Article
  19. BioMed research international · 2018
    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

2 authors at 2 institutions in 1 country.

H AngelakopoulosInfectious Disease Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
E L Hohmann
Harvard University · USMassachusetts General Hospital · US

Funding

ZD6416 Analgesic--Painful Distal Symmetrical PolyneuropaM01RR001066 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI BROWN, EMERY N · 1985 to 2008
$37.4M
PHOP/PHOQ DELETED S TYPHI VACCINE STRAINSR01AI045137 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI HOHMANN, ELIZABETH L. · 1999 to 2002
$790k
NCRR NIH HHS M01 RR001066NCRR NIH HHS MO1 RR01066-21NIAID NIH HHS R01AI45137
6 · The paper itself

Abstract

Attenuated Salmonella enterica serovar Typhi has been studied as an oral vaccine vector. Despite success with attenuated S. enterica serovar Typhimurium vectors in animals, early clinical trials of S. enterica serovar Typhi expressing heterologous antigens have shown that few subjects have detectable immune responses to vectored antigens. A previous clinical study of phoP/phoQ-deleted S. enterica serovar Typhi expressing Helicobacter pylori urease from a multicopy plasmid showed that none of eight subjects had detectable immune responses to the vectored antigen. In an attempt to further define the variables important for engendering immune responses to vectored antigens in humans, six volunteers were inoculated with 5 x 10(7) to 8 x 10(7) CFU of phoP/phoQ-deleted S. enterica serovar Typhimurium expressing the same antigen. Two of the six volunteers had fever; none had diarrhea, bacteremia, or other serious side effects. The volunteers were more durably colonized than in previous studies of phoP/phoQ-deleted S. enterica serovar Typhi. Five of the six volunteers seroconverted to S. enterica serovar Typhimurium antigens and had strong evidence of anti-Salmonella mucosal immune responses by enzyme-linked immunospot studies. Three of six (three of five who seroconverted to Salmonella) had immune responses in the most sensitive assay of urease-specific immunoglobulin production by blood mononuclear cells in vitro. One of these had a fourfold or greater increase in end-point immunoglobulin titer in serum versus urease. Attenuated S. enterica serovar Typhimurium appears to be more effective than S. enterica serovar Typhi for engendering immune responses to urease. Data suggest that this may be related to a greater stability of antigen-expressing plasmid in S. enterica serovar Typhimurium and/or prolonged intestinal colonization. Specific factors unique to nontyphoidal salmonellae may also be important for stimulation of the gastrointestinal immune system.

Indexed as

Administration, OralAdultAnimalsBacterial ProteinsBacterial VaccinesEnzyme-Linked Immunosorbent AssayFemaleHelicobacter pyloriHumansImmunoglobulin AImmunoglobulin GMaleMiceMucous MembraneMutationPilot ProjectsBacterial ProteinsBacterial VaccinesImmunoglobulin AImmunoglobulin GPhoP protein, BacteriaPhoQ protein, BacteriaUrease

Identifiers

PMID10722611
PMCPMC97395
OpenAlexW1977686084

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.