title: Enhanced protection against bovine tuberculosis after coadministration of Mycobacterium bovis BCG with a Mycobacterial protein vaccine-adjuvant combination but not after coadministration of adjuvant alone.
abstract: Current efforts are aimed at optimizing the protective efficacy of Mycobacterium bovis BCG by the use of vaccine combinations. We have recently demonstrated that the protection afforded by BCG alone is enhanced by vaccinating cattle with a combination of vaccines comprising BCG and a protein tuberculosis vaccine, namely, culture filtrate proteins (CFPs) from M. bovis plus an adjuvant. In the current study, three different adjuvant systems were compared. The CFP was formulated with a depot adjuvant, dimethyldioctadecyl ammonium bromide (DDA), together with one of three different immunostimulants: monophosphoryl lipid A (MPL), a synthetic mycobacterial phosphatidylinositol mannoside-2 (PIM2), and a synthetic lipopeptide (Pam3Cys-SKKKK [Pam(3)CSK(4)]). Groups of cattle (n = 10/group) were vaccinated with BCG-CFP-DDA-PIM2, BCG-CFP-DDA-MPL, or BCG-CFP-DDA-Pam(3)CSK(4). Two additional groups (n = 10) were vaccinated with BCG alone or BCG-adjuvant (DDA-MPL), and a control group was left unvaccinated. Protection was assessed by challenging the cattle intratracheally with M. bovis. Groups of cattle vaccinated with BCG-CFP-DDA-PIM2, BCG-CFP-DDA-MPL, BCG-CFP-DDA-Pam(3)CSK(4), and BCG alone showed significant reductions in three, three, five, and three pathological and microbiological disease parameters, respectively, compared to the results for the nonvaccinated group. Vaccination with the combination of BCG and the DDA-MPL adjuvant alone abrogated the protection conferred by BCG alone. The profiling of cytokine gene expression following vaccination, prior to challenge, did not illuminate significant differences which could explain the latter result. Vaccination of cattle with a combination of BCG and protein tuberculosis vaccine enhances protection against tuberculosis.
authors.affiliation: AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand. neil.wedlock@agresearch.co.nz
authors.forename: D Neil
authors.initials: DN
authors.lastname: Wedlock
authors.forename: Michel
authors.initials: M
authors.lastname: Denis
authors.forename: Gavin F
authors.initials: GF
authors.lastname: Painter
authors.forename: Gary D
authors.initials: GD
authors.lastname: Ainge
authors.forename: H Martin
authors.initials: HM
authors.lastname: Vordermeier
authors.forename: R Glyn
authors.initials: RG
authors.lastname: Hewinson
authors.forename: Bryce M
authors.initials: BM
authors.lastname: Buddle
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D009161:Mycobacterium / Q000276:immunology / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology; D014374:Tuberculin Test; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000517:prevention & control*; D014611:Vaccination / Q000662:veterinary*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines