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Veterinary microbiology2007; 125(1-2); 100-110; doi: 10.1016/j.vetmic.2007.05.007

Immunization by intrabronchial administration to 1-week-old foals of an unmarked double gene disruption strain of Rhodococcus equi strain 103+.

Abstract: Rhodococcus equi causes fatal granulomatous pneumonia in foals and immunocompromised animals and humans. However, there is no effective vaccine against this infection. In this study, the chromosomal genes isocitrate lyase (icl) and cholesterol oxidase (choE) were chosen as targets for mutation and assessment of the double mutant as an intrabronchial vaccine in 1-week-old foals. Using a modification of a suicide plasmid previously developed in this laboratory, we developed a choE-icl unmarked deletion mutant of R. equi strain 103+. Five 1-week-old foals were infected intrabronchially with the mutant and challenged intrabronchially with the parent, virulent, strain 2 weeks later. Three of the foals were protected against pneumonia caused by the virulent strain, but the other two foals developed pneumonia caused by the mutant strain during the post-challenge period. Since infection of 3-week-old foals by an icl mutant in an earlier study had shown complete attenuation of the strain, we conclude that a proportion of foals in the 1st week or so of life are predisposed to developing R. equi pneumonia because of an inability to mount an effective immune response. This has been suspected previously but this is the first time that this has been demonstrated experimentally.
Publication Date: 2007-05-18 PubMed ID: 17560744DOI: 10.1016/j.vetmic.2007.05.007Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research is about a study that aimed to create a vaccine against the bacteria Rhodococcus equi, which causes fatal lung disease in young horses and immune-compromised animals and humans. The researchers genetically modified the bacteria, tested its effectiveness as a vaccine, and discovered that some very young foals did not respond to the vaccine due to weak immune systems.

Study Overview

  • This research aimed to create a vaccine against the fatal pneumonia-causing bacteria, Rhodococcus equi. This bacteria is particular dangerous to one-week-old foals and other immune-compromised animals and humans. Given the absence of an effective vaccine against this infection, this study intended to genetically alter the bacteria to create a possible vaccine strain.

Methodology

  • The researchers selected two specific genes of the bacteria, isocitrate lyase (icl) and cholesterol oxidase (choE), and modified them with a method called suicide plasmid, which they previously developed in their laboratory. This resulted in the creation of a genetically-altered “mutant” strain of the bacteria.
  • The researchers then took five one-week-old foals and infected them with the genetically altered bacteria by introducing the bacteria directly into the bronchi of their lungs (intrabronchial administration).
  • Two weeks after infection with the modified bacteria strain, all foals were exposed to the unaltered, disease-causing bacteria strain. This would test the effectiveness of the mutant bacteria serving as a vaccine, with the expectation that the previous exposure would help the foals’ immune system to fight off the infection.

Results

  • Out of the five foals, three were successfully protected from developing pneumonia when later exposed to the unmodified, disease-causing strain. However, the other two foals developed pneumonia due to the genetically-altered bacteria that was initially used as the intended vaccine.
  • These results demonstrate that a proportion of very young foals do not have immune systems mature enough to effectively fight off the Rhodococcus equi bacteria, regardless of whether it has been genetically modified or not.

Study Conclusion

  • The researchers concluded that their vaccine strategy can work in a portion of foals, but some foals in their first week of life are too immune-compromised to respond effectively to the vaccine. They recommend further research to understand and address this immunity gap in very young foals.

Cite This Article

APA
Pei Y, Nicholson V, Woods K, Prescott JF. (2007). Immunization by intrabronchial administration to 1-week-old foals of an unmarked double gene disruption strain of Rhodococcus equi strain 103+. Vet Microbiol, 125(1-2), 100-110. https://doi.org/10.1016/j.vetmic.2007.05.007

Publication

ISSN: 0378-1135
NlmUniqueID: 7705469
Country: Netherlands
Language: English
Volume: 125
Issue: 1-2
Pages: 100-110

Researcher Affiliations

Pei, Yanlong
  • Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
Nicholson, Vivian
    Woods, Katharine
      Prescott, John F

        MeSH Terms

        • Actinomycetales Infections / immunology
        • Actinomycetales Infections / microbiology
        • Actinomycetales Infections / prevention & control
        • Actinomycetales Infections / veterinary
        • Animals
        • Animals, Newborn
        • Bacterial Vaccines / administration & dosage
        • Bacterial Vaccines / genetics
        • Bacterial Vaccines / immunology
        • Cholesterol Oxidase / genetics
        • DNA, Bacterial / genetics
        • Female
        • Horse Diseases / immunology
        • Horse Diseases / microbiology
        • Horse Diseases / prevention & control
        • Horses
        • Immunization / methods
        • Immunization / veterinary
        • Isocitrate Lyase / genetics
        • Mice
        • Plasmids / genetics
        • Pneumonia, Bacterial / immunology
        • Pneumonia, Bacterial / microbiology
        • Pneumonia, Bacterial / prevention & control
        • Pneumonia, Bacterial / veterinary
        • Rhodococcus equi / genetics
        • Rhodococcus equi / immunology
        • Sequence Deletion / immunology
        • Vaccines, Attenuated / administration & dosage
        • Vaccines, Attenuated / genetics
        • Vaccines, Attenuated / immunology

        Citations

        This article has been cited 11 times.
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