title: 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.
authors.affiliation: Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Pei
authors.forename: Vivian
authors.initials: V
authors.lastname: Nicholson
authors.forename: Katharine
authors.initials: K
authors.lastname: Woods
authors.forename: John F
authors.initials: JF
authors.lastname: Prescott
mesh_terms: D000193:Actinomycetales Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D000818:Animals; D000831:Animals, Newborn; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D002789:Cholesterol Oxidase / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D006734:Horse Diseases / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D006736:Horses; D007114:Immunization / Q000379:methods / Q000662:veterinary*; D007522:Isocitrate Lyase / Q000235:genetics; D051379:Mice; D010957:Plasmids / Q000235:genetics; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D016929:Rhodococcus equi / Q000235:genetics* / Q000276:immunology*; D017384:Sequence Deletion / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D014613:Vaccines, Attenuated; D002789:Cholesterol Oxidase; D007522:Isocitrate Lyase