Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates

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.

Effects of Inactivated Mycobacterium bovis Vaccination on Molokai-Origin Wild Pigs Experimentally Infected with Virulent M. bovis

“…Application of an orally-administered, heat-inactivated M. bovis vaccine to bovine tuberculosis-affected wild boar populations in Spain appears to have helped in reducing disease prevalence [8]. In addition, that vaccine preparation administered orally has shown some efficacy in protecting cattle and cervids, as well as goats and wild boar parenterally [9][10][11][12][13]. Here, we describe the use of heat-inactivated M. bovis vaccine in wild pigs of Molokai origin, and its efficacy against experimental infection with virulent M. bovis.…”

“…Average lesion score based on examination of 23 tissues; 2 Bilateral tissues were collected and total score from both tissues reported here;3 Caud, Caudal Lung Lobes;4 Cran, Cranial Lung Lobes;5 Card, Cardiac Lung Lobes;6 Acc, Accessory Lung Lobe;7 Mand, Mandibular Lymph Nodes;8 Superf Cerv, Superficial Cervical Lymph Nodes;9 Medias, Mediastinal Lymph Node;10 Tracheo-bronch, Tracheobronchial Lymph Nodes;11 Hep, Hepatic Lymph Node;12 Mes, Mesenteric Lymph Node;13 Shaded cells have at least one positive outcome.…”

Efficacy of parenteral vaccination against tuberculosis with heat-inactivated Mycobacterium bovis in experimentally challenged goats

“…The Heat-Inactivated Mycobacterium bovis (HIMB), is a new vaccine candidate that may rule out some constraints of live-attenuated vaccines [ 11 ]. The efficacy of HIMB has already been evaluated under experimental conditions in cattle [ 12 ], sheep [ 13 ], red deer [ 14 ] and wild boar [ 15 ] and, under field conditions in wild boar [ 16 ], yielding variable results.…”

Prevención y diagnóstico veterinario de la tuberculosis bovina. Una revisión de las tendencias globales

“…Una circunstancia que complica su obtención, es la comprobada heterogeneidad de respuestas observadas con las cepas vacunales BCG [24,25], la variedad de métodos para obtener formulaciones candidatas (vivas e inactivadas, tanto por vía química como por calor) [26] y el enmascaramiento que producen las micobacterias ambientales en la eficacia de BCG [27,28].…”

“…En los últimos años se han desarrollado estrategias para lograr una protección efectiva, estable y duradera contra la TBb (figura 1). Se mencionan esfuerzos como el uso de BCG viva e inactivada, con sus variantes de formulación-administración, incluyendo el uso de vacunas vectoriales recombinantes [26,31,32], vacunas vivas con atenuación genética [33], y las inductoras de respuesta inmune diferenciante entre animales infectados y vacunados (DIVA) [34].…”