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Clinical and Vaccine Immunology, May 2008, p. 765-772, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00034-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

D. Neil Wedlock,^1* Michel Denis,¹ Gavin F. Painter,² Gary D. Ainge,² H. Martin Vordermeier,³ R. Glyn Hewinson,³ and Bryce M. Buddle¹

AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand,¹ Industrial Research Limited, Carbohydrate Chemistry, P.O. Box 31-310, Lower Hutt, New Zealand,² Veterinary Laboratory Agency, Weybridge, Surrey, United Kingdom³

Received 27 January 2008/ Returned for modification 15 February 2008/ Accepted 4 March 2008

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 [Pam₃CSK₄]). Groups of cattle (n = 10/group) were vaccinated with BCG-CFP-DDA-PIM2, BCG-CFP-DDA-MPL, or BCG-CFP-DDA-Pam₃CSK₄. 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-Pam₃CSK₄, 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.

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* Corresponding author. Mailing address: AgResearch Limited, Hopkirk Research Institute, Grasslands Research Centre, Private Bag 11008, Palmerston North, New Zealand. Phone: 64 6 3518698. Fax: 64 6 3537853. E-mail: neil.wedlock{at}agresearch.co.nz

Published ahead of print on 12 March 2008.

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Clinical and Vaccine Immunology, May 2008, p. 765-772, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00034-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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