title: Development of an unbiased antigen-mining approach to identify novel vaccine antigens and diagnostic reagents for bovine tuberculosis.
abstract: Previous experiments for the identification of novel diagnostic or vaccine candidates for bovine tuberculosis have followed a targeted approach, wherein specific groups of proteins suspected to contain likely candidates are prioritized for immunological assessment (for example, with in silico approaches). However, a disadvantage of this approach is that the sets of proteins analyzed are restricted by the initial selection criteria. In this paper, we describe a series of experiments to evaluate a nonbiased approach to antigen mining by utilizing a Gateway clone set for Mycobacterium tuberculosis, which constitutes a library of clones expressing 3,294 M. tuberculosis proteins. Although whole-blood culture experiments using Mycobacterium bovis-infected animals and M. bovis BCG-vaccinated controls did not reveal proteins capable of differential diagnosis, several novel immunogenic proteins were identified and prioritized for efficacy studies in a murine vaccination/challenge model. These results demonstrate that Rv3329-immunized mice had lower bacterial cell counts in their spleens following challenge with M. bovis. In conclusion, we demonstrate that this nonbiased approach to antigen mining is a useful tool for identifying and prioritizing novel proteins for further assessment as vaccine antigens.
authors.affiliation: Department of Bovine Tuberculosis, Animal Health and Veterinary Laboratories Agency, Surrey, United Kingdom.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Jones
authors.forename: Bhagwati L
authors.initials: BL
authors.lastname: Khatri
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Garcia-Pelayo
authors.forename: Daryan A
authors.initials: DA
authors.lastname: Kaveh
authors.forename: Véronique S
authors.initials: VS
authors.lastname: Bachy
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hogarth
authors.forename: Esen
authors.initials: E
authors.lastname: Wooff
authors.forename: Paul
authors.initials: P
authors.lastname: Golby
authors.forename: H Martin
authors.initials: HM
authors.lastname: Vordermeier
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D002417:Cattle; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D014380:Tuberculosis, Bovine / Q000175:diagnosis* / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines