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Infection and Immunity, June 2005, p. 3540-3546, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3540-3546.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Vaccination of Cattle with a CpG Oligodeoxynucleotide-Formulated Mycobacterial Protein Vaccine and Mycobacterium bovis BCG Induces Levels of Protection against Bovine Tuberculosis Superior to Those Induced by Vaccination with BCG Alone

D. Neil Wedlock,1* Michel Denis,1 Margot A. Skinner,1,{dagger} Jessica Koach,1 Geoffrey W. de Lisle,1 H. Martin Vordermeier,2 R. Glyn Hewinson,2 Sylvia van Drunen Littel-van den Hurk,3 Lorne A. Babiuk,3 Rolf Hecker,4 and Bryce M. Buddle1

AgResearch, Wallaceville Animal Research Centre, Upper Hutt, New Zealand,1 VLA, Weybridge, United Kingdom,2 Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada,3 QIAGEN, Hilden, Germany4

Received 11 November 2004/ Returned for modification 22 December 2004/ Accepted 28 January 2005

The development of a subunit protein vaccine for bovine tuberculosis which could be used either in combination with Mycobacterium bovis BCG (to improve the efficacy of that vaccine) or alone would offer significant advantages over currently available strategies. A study was conducted with cattle to determine the protective efficacy of a strategy based on concurrent immunization with an M. bovis culture filtrate (CFP) vaccine and BCG compared to vaccination with either vaccine alone. One group of calves (10 animals per group) was vaccinated subcutaneously with CFP formulated with Emulsigen and combined with a CpG oligodeoxynucleotide (ODN). A second group was vaccinated with both the CFP vaccine and BCG injected at adjacent sites (CFP-BCG). One further group was vaccinated subcutaneously with BCG, while another group served as nonvaccinated control animals. Vaccination with CFP-BCG induced levels of antigen-specific gamma interferon (IFN-{gamma}) and interleukin-2 (IL-2) in whole-blood cultures that were higher than those induced by vaccination with BCG alone. The combination of CFP and BCG did not enhance the production of antibodies to M. bovis CFP compared to vaccination with CFP alone. Vaccination with CFP alone led to delayed antigen-specific IFN-{gamma} and IL-2 responses. Vaccination with CFP-BCG induced a high level of protection against an intratracheal challenge with virulent M. bovis, based on a significant enhancement of six pathological and microbiological parameters of protection compared with the nonvaccinated group. In contrast, vaccination with BCG alone induced a significant enhancement of protection in only one parameter, while CFP alone induced no protection. These results suggest that a combination of a CpG ODN-formulated protein vaccine and BCG offers better protection against bovine tuberculosis than does BCG alone.

* Corresponding author. Mailing address: AgResearch, Wallaceville Animal Research Centre, P. O. Box 40063, Upper Hutt, New Zealand. Phone: 64 4 5290593. Fax: 64 4 5290380. E-mail: neil.wedlock{at}agresearch.co.nz.

Editor: J. L. Flynn

{dagger} Present address: HortResearch Bioscience, Mount Albert, Auckland, New Zealand.

Infection and Immunity, June 2005, p. 3540-3546, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3540-3546.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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