Evidence map›Paper›PMID 19368784›Full record

ArticleVaccine2009

Characterization of rationally attenuated Francisella tularensis vaccine strains that harbor deletions in the guaA and guaB genes.

Araceli E Santiago, Leah E Cole, Augusto Franco, Stefanie N Vogel, Myron M Levine, Eileen M Barry

Abstract read
In one paragraph

Article in Vaccine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
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

33 citing papers in PubMed.

  1. Infection and immunity · 2025
    Article
  2. Article
  3. Review
  4. A journey into the regulatory secrets of theFrontiers in pharmacology · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Tularemia vaccines.Folia microbiologica · 2016
    Review
  13. Article
  14. Article
  15. Article
  16. Signature-tagged mutagenesis of Vibrio vulnificus.The Journal of veterinary medical science · 2015
    Article
  17. Article
  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

6 authors.

Araceli E SantiagoCenter for Vaccine Development, University of Maryland, Baltimore, 21201, United States.
Leah E Cole
Augusto Franco
Stefanie N Vogel
Myron M Levine
Eileen M Barry

Funding

Vaccine strategy for broad spectrum protection agains non-typhoidal salmonellU54AI057168 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI BARRY, EILEEN M. · 2003 to 2013
$91.5M
Advancement of New Live Attenuated F. Tularensis Type A Vaccine StrainsU01AI077909 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI BARRY, EILEEN M. · 2009 to 2010
$1.1M
NIAID NIH HHS U01 AI077909NIAID NIH HHS U54 AI057168NIAID NIH HHS U54 AI57168
6 · The paper itself

Abstract

Francisella tularensis, the etiologic agent of tularemia, can cause severe and fatal infection after inhalation of as few as 10 -- 100CFU. F. tularensis is a potential bioterrorism agent and, therefore, a priority for countermeasure development. Vaccination with the live vaccine strain (LVS), developed from a Type B strain, confers partial protection against aerosal exposure to the more virulent Type A strains and provides proof of principle that a live attenuated vaccine strain may be efficacious. However LVS suffers from several notable drawbacks that have prevented its licensure and widespread use. To address the specific deficiencies that render LVS a sub-optimal tularemia vaccine, we engineered F. tularensis LVS strains with targeted deletions in the guaA or guaB genes that encode critical enzymes in the guanine nucleotide biosynthetic pathway. F. tularensis LVSDeltaguaA and LVSDeltaguaB mutants were guanine auxotrophs and were highly attenuated in a mouse model of infection. While the mutants failed to replicate in macrophages, a robust proinflammatory cytokine response, equivalent to that of the parental LVS, was elicited. Mice vaccinated with a single dose of the F. tularensis LVSDeltaguaA or LVSDeltaguaB mutant were fully protected against subsequent lethal challenge with the LVS parental strain. These findings suggest the specific deletion of these target genes could generate a safe and efficacious live attenuated vaccine.

Indexed as

AnimalsBacterial VaccinesBase SequenceCarbon-Nitrogen LigasesCytokinesFrancisella tularensisGene DeletionGuanineIMP DehydrogenaseMacrophagesMiceMice, Inbred BALB CMice, Inbred C57BLMolecular Sequence DataToll-Like Receptor 2Vaccines, AttenuatedBacterial VaccinesCarbon-Nitrogen LigasesCytokinesGMP synthase (glutamine-hydrolyzing)GuanineIMP DehydrogenaseTlr2 protein, mouseToll-Like Receptor 2Vaccines, AttenuatedVaccines, Synthetic

Identifiers

PMID19368784
PMCPMC2716139

What OpenQuestion holds

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Registered trials

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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.