Instituto de Agrobiotecnología y Biología Molecular, (IABIMO) INTA-CONICET, Argentina; Instituto de Biotecnología, CICVyA, Instituto Nacional de Tecnología Agropecuaria N. Repetto and De los Reseros, Hurlingham, 1686, Buenos Aires, Argentina.
Tuberculosis (Edinb). 2024 Dec;149:102574. doi: 10.1016/j.tube.2024.102574. Epub 2024 Nov 1.
A vaccine for bovine tuberculosis is urgently needed. The BCG vaccine (the Bacille Calmette-Guérin), currently the only licensed vaccine for tuberculosis in humans, offers variable protection in cattle. However, BCG is a highly safe vaccine, and any alternative vaccine must not only offer greater protection than BCG but also match and improve its safety profile. Mice are the most widely used animal models in tuberculosis research, particularly for pre-clinical vaccine evaluation. In these animal models, the key indicator of infection or vaccine efficacy is the mycobacteria load in the lungs. In this study, we evaluated the long-term protection conferred by vaccinating BALB/c mice with a Mycobacterium bovis triple mutant lacking the virulence genes phoP, esxA, and esxB. Our findings showed that the triple mutant protected the lungs of mice against M. bovis challenge for up to one-year post-vaccination. However, the bacterial load in the spleens predominantly comprised the vaccine strain, and the lungs also contained some of these bacteria. These results suggest that the vaccine strain persisted in the mouse organs for at least one year, which raised concerns about its potential safety for animal vaccination.
急需一种牛型结核疫苗。卡介苗（BCG）是目前人类唯一获准用于结核病的疫苗，但其在牛中的保护效果参差不齐。然而，BCG 是一种高度安全的疫苗，任何替代疫苗不仅必须提供比 BCG 更好的保护，而且还必须与其安全性相匹配并得到改善。小鼠是结核病研究中最广泛使用的动物模型，特别是用于临床前疫苗评估。在这些动物模型中，感染或疫苗效力的关键指标是肺部的分枝杆菌负荷。在这项研究中，我们评估了用缺乏毒力基因 phoP、esxA 和 esxB 的牛分枝杆菌三重突变体疫苗接种 BALB/c 小鼠所带来的长期保护作用。我们的研究结果表明，三重突变体可在接种疫苗后长达一年的时间内保护小鼠免受牛分枝杆菌的攻击。然而，脾脏中的细菌负荷主要由疫苗株组成，肺部也含有一些这些细菌。这些结果表明，疫苗株在小鼠器官中至少持续存在一年，这引发了对其用于动物接种的潜在安全性的担忧。
