Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines

AgResearch, Hopkirk Research Institute, Grasslands Research Centre, Private Bag 11008, Palmerston North 4442, New Zealand.
Veterinary Immunology and Immunopathology (Impact Factor: 1.54). 12/2011; 144(3-4):220-7. DOI: 10.1016/j.vetimm.2011.09.005
Source: PubMed


Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral BCG did not enhance the protection conferred by administration of oral BCG alone.

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    • "Due to the severity of the M. bovis infection induced by experimental challenge, it has been critical to use lung and pulmonary lymph node lesion scores to assess protection. Scores of 0–5 have been used to quantify lung lesion severity and have been used for individual lung lobes and then pooled (Vordermeier et al., 2002) or a score of 0–5 based on total count of lesions in the lungs (Wedlock et al., 2011). In addition, lesion scores of 0–3 have been used to assess the severity of lesions in individual pulmonary lymph nodes and scores pooled for all pulmonary lymph nodes. "
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    • "Studies have been undertaken to test different doses of oral administrated BCG to determine whether a dose of BCG could be identified that induced protection but did not induce tuberculin skin test reactivity. In the first study, doses of 1 9 10 7 or lower were not effective at inducing protective immunity or a tuberculin skin test reactivity (Wedlock et al., 2011). In contrast, in a second study, a slightly higher oral dose of 2 9 10 7 CFU of BCG was as effective as a 10-fold higher dose in protecting calves against a M. bovis challenge and there were fewer positive skin test responses (Buddle et al., 2011). "
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