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.