title: Efficacy and immunogenicity of Mycobacterium bovis DeltaRD1 against aerosol M. bovis infection in neonatal calves.
abstract: An attenuated Mycobacterium bovisRD1 deletion (DeltaRD1) mutant of the Ravenel strain was constructed, characterized, and sequenced. This M. bovis DeltaRD1 vaccine strain administered to calves at 2 weeks of age provided similar efficacy as M. bovis bacillus Calmette Guerin (BCG) against low dose, aerosol challenge with virulent M. bovis at 3.5 months of age. Approximately 4.5 months after challenge, both DeltaRD1- and BCG-vaccinates had reduced tuberculosis (TB)-associated pathology in lungs and lung-associated lymph nodes and M. bovis colonization of tracheobronchial lymph nodes as compared to non-vaccinates. Mean central memory responses elicited by either DeltaRD1 or BCG prior to challenge correlated with reduced pathology and bacterial colonization. Neither DeltaRD1 or BCG elicited IFN-gamma responses to rESAT-6:CFP-10 prior to challenge, an emerging tool for modern TB surveillance programs. The DeltaRD1 strain may prove useful for bovine TB vaccine programs, particularly if additional mutations are included to improve safety and immunogenicity.
authors.affiliation: National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA 50010, USA. ray.waters@ars.usda.gov
authors.forename: W Ray
authors.initials: WR
authors.lastname: Waters
authors.forename: Mitchell V
authors.initials: MV
authors.lastname: Palmer
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nonnecke
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Thacker
authors.forename: Charles F Capinos
authors.initials: CF
authors.lastname: Scherer
authors.forename: D Mark
authors.initials: DM
authors.lastname: Estes
authors.forename: R Glyn
authors.initials: RG
authors.lastname: Hewinson
authors.forename: H Martin
authors.initials: HM
authors.lastname: Vordermeier
authors.forename: S Whitney
authors.initials: SW
authors.lastname: Barnes
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Federe
authors.forename: John R
authors.initials: JR
authors.lastname: Walker
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Glynne
authors.forename: Tsungda
authors.initials: T
authors.lastname: Hsu
authors.forename: Brian
authors.initials: B
authors.lastname: Weinrick
authors.forename: Karolin
authors.initials: K
authors.lastname: Biermann
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Larsen
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
mesh_terms: D000336:Aerosols; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D007156:Immunologic Memory; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009163:Mycobacterium bovis / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D016019:Survival Analysis; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D000336:Aerosols; D004269:DNA, Bacterial; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated