Tree J A, Williams A, Clark S, Hall G, Marsh P D, Ivanyi J
Health Protection Agency, Porton Down, Centre for Applied Microbiology and Research, Salisbury, Wiltshire, UK.
Clin Exp Immunol. 2004 Dec;138(3):405-9. doi: 10.1111/j.1365-2249.2004.02648.x.
Intranasal vaccination may offer practical benefits and better protection against respiratory infections, including tuberculosis. In this paper, we investigated the persistence of the Mycobacterium bovis-strain bacille Calmette-Guerin (BCG) Pasteur, lung granuloma formation and protection against pathogenic tuberculous challenge in mice. A pronounced BCG dose-dependent granulomatous infiltration of the lungs was observed following intranasal, but not after subcutaneous, vaccination. Corresponding doses of BCG, over a 100-fold range, imparted similar protection against H37Rv challenge when comparing the intranasal and subcutaneous vaccination routes. Interestingly, a BCG dose-dependent reduction of the H37Rv challenge infection was observed in the lungs, but not in the spleens, following both intranasal and subcutaneous vaccination. In the light of the observed concurrence between the extent of granuloma formation and the level of protection of the lungs, we conclude that intranasal vaccination leading to best protective efficacy needs to be balanced with an acceptable safety margin avoiding undue pathology in the lungs.
鼻内接种疫苗可能具有实际益处，并能更好地预防包括结核病在内的呼吸道感染。在本文中，我们研究了牛分枝杆菌卡介苗（BCG）巴斯德菌株在小鼠体内的持久性、肺部肉芽肿形成以及对致病性结核攻击的保护作用。鼻内接种后，而非皮下接种后，观察到肺部出现明显的卡介苗剂量依赖性肉芽肿浸润。在比较鼻内和皮下接种途径时，100倍范围内相应剂量的卡介苗对H37Rv攻击提供了相似的保护作用。有趣的是，鼻内和皮下接种后，在肺部观察到卡介苗剂量依赖性降低H37Rv攻击感染，但在脾脏中未观察到。鉴于观察到的肉芽肿形成程度与肺部保护水平之间的一致性，我们得出结论，导致最佳保护效果的鼻内接种需要与可接受的安全边际相平衡，以避免肺部出现过度病理变化。
