Evidence map›Paper›PMID 19884333›Full record

ArticleInfection and immunity2010

A new generation of stable, nonantibiotic, low-copy-number plasmids improves immune responses to foreign antigens in Salmonella enterica serovar Typhi live vectors.

James E Galen, Jin Yuan Wang, Magaly Chinchilla, Christopher Vindurampulle, Jeffrey E Vogel, Haim Levy, William C Blackwelder, Marcela F Pasetti, Myron M Levine

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
7.1field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 42 citations in OpenAlex.

  1. Characterization of the role of putativeJournal of bacteriology · 2026
    Article
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  4. Review
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  6. Regulated DelayedTheranostics · 2019
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
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  14. Salmonella as a vaccine delivery vehicle.Expert review of vaccines · 2013
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
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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

9 authors at 1 institution in 2 countries.

James E GalenCenter for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., HSF Bldg. I, Rm. 480, Baltimore, MD 21201, USA. jgalen@medicine.umaryland.edu
Jin Yuan Wang
Magaly Chinchilla
Christopher Vindurampulle
Jeffrey E Vogel
Haim Levy
William C Blackwelder
Marcela F Pasetti
Myron M Levine
University of Maryland, Baltimore · US

Funding

Vaccine strategy for broad spectrum protection agains non-typhoidal salmonellU54AI057168 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI LEVINE, MYRON MAX · 2003 to 2013
$91.5M
RECOMBINANT &LIVE ORAL SALMONELLA TYPHI HYBRID VACCINESR01AI029471 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI LEVINE, MYRON MAX · 1990 to 2008
$3.7M
CONTROL MESURES IN AGING AND INFECTIOUS DISEASEN01AI045251 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI LEVINE, MYRON MAX · 1994 to 2000
–
NIAID NIH HHS 5 RO1 AI29471NIAID NIH HHS N01 AI45251NIAID NIH HHS R01 AI029471NIAID NIH HHS U54 AI057168NIAID NIH HHS U54 AI57168
6 · The paper itself

Abstract

We hypothesized that adequately engineered attenuated Salmonella enterica serovar Typhi strains can serve as multivalent mucosal live vector vaccines to immunize against unrelated human pathogens. Toward this ultimate goal, we have developed a novel genetic stabilization system for antigen-expressing plasmids, engineered to encode the single-stranded binding protein (SSB), an essential protein involved in DNA metabolism which was deleted from the live vector chromosome. We utilized full-length protective antigen (PA83) of anthrax toxin from Bacillus anthracis as a foreign antigen and expressed PA83 as a fusion with the ClyA export protein, which allows export of ClyA-PA83 to the surface of S. Typhi live vectors. A series of SSB-encoding multicopy expression plasmids were introduced into reengineered S. Typhi strains previously tested in clinical trials, i.e., CVD 908-htrA and its less attenuated parent CVD 908. Immunogenicity was examined using a mouse model of intranasal immunization with live vector, followed by parenteral boosting with purified PA83. PA-specific antibody responses markedly improved as the copy number of the SSB-encoding plasmids decreased, and this effect was dramatically enhanced when the foreign antigen was delivered by the less attenuated live vector CVD 908ssb. These results suggest that antibody responses to antigens delivered by S. Typhi live vectors are inversely related to the metabolic burden imposed by expression of the foreign antigen and that these responses can be improved when antigens are expressed from low-copy-number plasmids and exported out of the cytoplasm of less attenuated live vectors.

Indexed as

AnimalsAntigens, BacterialBacterial ProteinsBacterial VaccinesDNA, Single-StrandedGene Expression Regulation, BacterialHumansImmunity, MucosalMiceMutagenesisPlasmidsProtein BindingProtein EngineeringSalmonella Infections, AnimalSalmonella typhiVaccines, SyntheticAntigens, BacterialBacterial ProteinsBacterial VaccinesDNA, Single-StrandedVaccines, Synthetic

Identifiers

PMID19884333
PMCPMC2798174
OpenAlexW2133264375

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.