Abstract
Conventional control and eradication strategies for bovine tuberculosis (BTB) face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle.Twenty-four mixed breed calves (Bos taurus) aged 4–6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331), formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control). Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG.The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group.In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study, urging further evaluation of the vaccine in challenge studies using virulent M. bovis and assessment of vaccine efficacy in field conditions.
Highlights
Control of bovine tuberculosis (BTB), caused by Mycobacterium bovis (M. bovis), is urgently needed on a global scale
The only available vaccine is that produced with the Bacille Calmette-Guerin (BCG) strain, which originated from virulent M. bovis through attenuation and was first used in humans in 1921 [5, 6]
One animal from the formalin-inactivated BCG group was excluded from this analysis due to unresponsiveness of white blood cells to stimulation with pokeweed mitogen (PWM) from T1 to T9
Summary
Control of bovine tuberculosis (BTB), caused by Mycobacterium bovis (M. bovis), is urgently needed on a global scale. Research efforts have focused on the development of diagnostic reagents that can differentiate between infected and vaccinated animals (DIVA) and on potentiation of the protective effect of BCG [8]. Different strategies using live BCG as either the priming or boosting vaccine in combination with a viral vector [9], recombinant DNA or sub-unit vaccine formulations [10] incorporating various Mycobacterium tuberculosis complex (MTBC) specific antigens, have been explored, with conflicting results. Skinner et al [11] found that the use of a DNA primeBCG boost regimen using plasmids encoding Hsp, Hsp and Apa was able to significantly improve protection against BTB compared to BCG alone. A study by Vordermeier et al [9], showed that the efficacy of BCG seemed to improve after boosting with a formulation of recombinant attenuated adenovirus expressing antigen 85A. Vaccination with MPB70 or MPB83 DNA plasmids was not found to be protective in cattle [12]
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