Balseiro Ana, Altuzarra Raúl, Vidal Enric, Moll Xavier, Espada Yvonne, Sevilla Iker A, Domingo Mariano, Garrido Joseba M, Juste Ramón A, Prieto Miguel, Pérez de Val Bernat
SERIDA, Servicio Regional de Investigación y Desarrollo Agroalimentario, Centro de Biotecnología Animal, Gijón, Asturias, Spain.
Departament de Medicina i Cirugia Animals, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Catalonia, Spain.
PLoS One. 2017 Jul 5;12(7):e0180546. doi: 10.1371/journal.pone.0180546. eCollection 2017.
BACKGROUND/AIMS: Animal tuberculosis (TB) is a complex animal health problem that causes disruption to trade and significant economic losses. TB involves a multi-host system where sheep, traditionally considered a rare host of this infection, have been recently included. The aims of this study were to develop an experimental TB infection model in sheep with a Mycobacterium caprae field strain isolated from a tuberculous diseased ewe, and to use this to evaluate the safety and efficacy of two vaccines against TB in sheep, the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine.
Eighteen 2 month-old lambs were experimentally challenged with M. caprae by the endotracheal route (1.5 × 103 CFU). They were separated per treatment group into parenterally vaccinated with a live BCG Danish strain vaccine (n = 6), orally vaccinated with a suspension of HIMB (n = 6) and unvaccinated controls (n = 6). Clinical, immunological, pathological and bacteriological parameters of infection were measured.
All lambs were successfully infected and developed gross TB lesions in the respiratory system. The BCG vaccine conferred considerable protection against experimental TB in lambs, as measured by a reduction of the gross lesion volumes and bacterial load. However, HIMB vaccinated animals did not show protection.
This study proposes a reliable new experimental model for a better understanding of tuberculosis in sheep. BCG vaccination offers an effective prospect for controlling the disease. Moreover alternative doses and/or routes of administration should be considered to evaluate the efficacy of the HIMB vaccine candidate.
背景/目的：动物结核病是一个复杂的动物健康问题，会扰乱贸易并造成重大经济损失。结核病涉及一个多宿主系统，传统上被认为是这种感染罕见宿主的绵羊最近也被纳入其中。本研究的目的是用从患结核病的母羊分离出的山羊分枝杆菌田间菌株建立绵羊实验性结核病感染模型，并利用该模型评估两种抗绵羊结核病疫苗的安全性和有效性，即减毒活牛分枝杆菌卡介苗（丹麦菌株）和热灭活牛分枝杆菌（HIMB）疫苗。
18只2月龄羔羊通过气管内途径用山羊分枝杆菌进行实验性攻击（1.5×10³CFU）。它们按治疗组分为经皮下接种减毒活丹麦卡介苗疫苗的组（n = 6）、经口服接种HIMB悬液的组（n = 6）和未接种疫苗的对照组（n = 6）。测量感染的临床、免疫、病理和细菌学参数。
所有羔羊均成功感染并在呼吸系统出现明显的结核病变。通过测量病变总体积和细菌载量发现，卡介苗疫苗对羔羊实验性结核病提供了相当程度的保护。然而，接种HIMB疫苗的动物未显示出保护作用。
本研究提出了一个可靠的新实验模型，以更好地了解绵羊结核病。卡介苗接种为控制该病提供了有效的前景。此外，应考虑替代剂量和/或给药途径来评估HIMB候选疫苗的疗效。
