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.
"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. "
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis either caused by Mycobacterium bovis or M. caprae is a significant burden to agricultural industries worldwide. Vaccination of domestic ruminant species such as cattle and goats constitutes a potential tool to support disease control. This review will discuss recent progress made to develop tuberculosis vaccines against domestic ruminants as well as approaches to differentiate vaccinated and infected animals (DIVA) and biomarker discovery studies.
Research in Veterinary Science 05/2014; 97. DOI:10.1016/j.rvsc.2014.04.015 · 1.41 Impact Factor
"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). "
[Show abstract][Hide abstract] ABSTRACT: Vaccination is a key strategy for control of tuberculosis (TB), and considerable progress has been made in the past 5 years to develop improved vaccines for humans and animals, differentiate vaccinated animals from those infected with Mycobacterium bovis and deliver vaccines to wildlife. Studies have moved from testing vaccines in small animal models to clinical trials in humans and from experimental challenge studies in cattle and wildlife to evaluation of vaccines in the field. Candidate vaccines undergoing testing in humans include live mycobacterial vaccines to replace bacille Calmette Guérin (BCG), subunit vaccines (virus vector or protein) to boost BCG and therapeutic vaccines used as an adjunct to chemotherapy. In cattle, a number of diagnostic tests have been developed and successfully tested for differentiating infected from vaccinated animals, which will facilitate the use of BCG vaccine in cattle. Encouraging results have been obtained from recent field trials in cattle using BCG vaccine to protect against natural exposure to M. bovis. To date, no subunit TB vaccines have induced improved protection compared with that for BCG, but prime–boost combinations of BCG with DNA, protein or virus-vectored vaccines have induced better protection than BCG vaccine alone. Development of an oral bait BCG formulation has demonstrated the practicality of delivering TB vaccines to wildlife. Oral BCG preparations have induced protection against experimental challenge of M. bovis in possums, badgers, wild boar and white-tailed deer and against natural exposure to M. bovis in possums. Recent progress in TB vaccine development has provided much impetus for their future use.
[Show abstract][Hide abstract] ABSTRACT: Vaccination has been spectacularly successful in eradicating or controlling some infectious diseases, and is particularly attractive as an approach to tackling other infectious diseases. Although vaccination against tuberculosis has been done for nearly 100years, it is clearly not that successful since the disease still occurs at epidemic levels in animals and humans in many areas. New approaches to vaccination against TB in humans and animals are currently in the pipeline, but none show either complete protection or sterilization. However, there is evidence to suggest that vaccination may deliver some positive outcomes. Not only should we be investigating new vaccines, but also how vaccines and candidates are used and delivered. There are many reasons to think that this task will not be simple, or perhaps not possible in some cases. We present different aspects of the development of vaccines against TB, outline some complications and suggest some new ways to consider this problem.
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