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Clin. Vaccine Immunol. doi:10.1128/CVI.00034-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Protection against bovine tuberculosis induced by BCG is enhanced by co-administration of adjuvanted mycobacterial protein vaccine, but abrogated by co-administration of adjuvant alone

AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand; Industrial Research Limited, Carbohydrate Chemistry, PO Box 31-310, Lower Hutt, New Zealand; Veterinary Laboratory Agency, Weybridge, Surrey, UK

^* To whom correspondence should be addressed. Email: neil.wedlock{at}agresearch.co.nz.

	Abstract

Current efforts are aimed at optimising the protective efficacy of BCG, via the use of vaccine combinations. We have recently demonstrated that 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 (CFP) 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: Pam₃CSK₄). Groups of cattle (n=10/group) were vaccinated with BCG + CFP/DDA/PIM-2, BCG + CFP/DDA/MPL or BCG + CFP/DDA/ Pam₃CSK₄. Two additional groups (n=10) were vaccinated with BCG alone, 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/PIM, BCG + CFP/DDA/MPL, BCG + CFP/DDA/ Pam₃CSK₄ and BCG alone showed significant reductions in three, three, five and three pathological and microbiological disease parameters respectively, compared to the non-vaccinated group. Combining vaccination of BCG with DDA/MPL adjuvant alone abrogated the protection conferred by BCG alone. Profiling cytokine gene expression following vaccination, prior to challenge, did not illuminate significant differences which could explain this latter result. Vaccination of cattle with a combination of BCG and protein tuberculosis vaccine enhances protection against tuberculosis.