Niroula Nirajan, Ghodasara Priya, Marreros Nelson, Fuller Bailey, Sanderson Haley, Zriba Slim, Walker Stew, Shury Todd K, Chen Jeffrey M
Parks Canada Agency, Government of Canada, Gatineau, Quebec, Canada.
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada.
Sci Rep. 2025 Jan 30;15(1):3764. doi: 10.1038/s41598-025-88176-0.
Bovine tuberculosis (BTB) is an infectious disease of livestock and wildlife species that is caused by pathogenic members of the Mycobacterium tuberculosis complex such as Mycobacterium bovis. Due to the introduction of M. bovis-infected bison in the 1920s, BTB is now endemic in wood bison (Bison bison athabascae) population within the Wood Buffalo National Park (WBNP) in northern Canada. This disease poses a grave threat to the long-term survival of this ecologically and culturally important species and has the potential to cause zoonotic TB and spill over to BTB-free livestock and other bison herds that live in the surrounding areas. Thus, effective BTB control strategies in WBNP bison are urgently needed. To this end, we aerosol challenged young bison with different doses of virulent M. bovis and observed disease-associated delayed-type hypersensitivity, gross lung and lymph node pathology and histopathology, as well as M. bovis burden in target organs, thus confirming the establishment of BTB in challenged animals. We then assessed the safety and efficacy of oral live BCG versus oral heat-inactivated M. bovis (HIMB) given in a homologous prime-boost regimen in bison. While both BCG and HIMB offered protection against BTB, BCG-treated bison thrived more, presented with fewer lung lesions at necropsy and lower burden of virulent M. bovis than HIMB-treated animals. Strikingly, oral HIMB induced almost no delayed-type hypersensitivity to intradermal tuberculin while oral live BCG induced very low sensitivity to tuberculin in bison, indicating their potential as DIVA (differentiating infected from vaccinated animals) vaccines for use in this important wildlife species.
牛结核病（BTB）是一种由结核分枝杆菌复合群的致病成员（如牛分枝杆菌）引起的家畜和野生动物传染病。由于在20世纪20年代引入了感染牛分枝杆菌的野牛，牛结核病现在在加拿大北部伍德布法罗国家公园（WBNP）的林地野牛（Bison bison athabascae）种群中呈地方性流行。这种疾病对这一具有重要生态和文化意义的物种的长期生存构成了严重威胁，并有导致人畜共患结核病的可能性，并可能传播到周边地区未感染牛结核病的家畜和其他野牛群中。因此，迫切需要在WBNP野牛中采取有效的牛结核病控制策略。为此，我们用不同剂量的强毒牛分枝杆菌对幼年野牛进行气溶胶攻击，并观察与疾病相关的迟发型超敏反应、肺部和淋巴结大体病理及组织病理学，以及靶器官中的牛分枝杆菌载量，从而证实了在受攻击动物中牛结核病的发生。然后，我们评估了口服活卡介苗与口服热灭活牛分枝杆菌（HIMB）在野牛同源初免-加强免疫方案中的安全性和有效性。虽然卡介苗和HIMB都能提供针对牛结核病的保护，但卡介苗治疗的野牛生长得更好，尸检时肺部病变较少，强毒牛分枝杆菌载量低于HIMB治疗的动物。引人注目的是，口服HIMB对皮内结核菌素几乎不诱导迟发型超敏反应，而口服活卡介苗在野牛中对结核菌素诱导的敏感性非常低，这表明它们作为用于这一重要野生动物物种的鉴别诊断疫苗（DIVA，区分感染动物和接种疫苗动物）的潜力。
