Hewinson R G, Vordermeier H M, Buddle B M
TB Research Group, Department of Bacterial Diseases, VLA Weybridge, Addlestone, Surrey KT15 3NB, UK.
Tuberculosis (Edinb). 2003;83(1-3):119-30. doi: 10.1016/s1472-9792(02)00062-8.
Over the past few years there has been a resurgence in research into bovine tuberculosis due to the sharp rise of the disease in countries such as Great Britain and to the continuing problem of wild-life reservoirs in countries such as New Zealand. One of the goals of this research is to develop cattle vaccines against TB. The initial testing of candidate vaccines is carried out in laboratory animals, initially mice and subsequently guinea pigs. A unique feature of the cattle vaccination programme is that candidate vaccines which show promise in laboratory models can then be tested in the natural host species, cattle, before progressing to clinical trials. This is a major advantage over the strategy for developing a vaccine for human tuberculosis where, of course, it is impossible to test a candidate vaccine by experimentally challenging the host species with the pathogen. The most commonly used model for testing vaccine candidates in cattle consists of an intra-tracheal challenge of between 10(3) and 10(4) colony forming units of Mycobacterium bovis. The pathology observed following challenge is similar to human tuberculosis giving rise to a marked granulomatous reaction and a predominantly cellular immune response. Using this model we have been able to make a number of significant advances towards a bovine TB vaccine. First we have developed antigen cocktails that, when used in a whole blood gamma interferon assay, can differentiate between M. bovis infected and BCG vaccinated animals. Next we have developed immune correlates of pathology, which allow us to assess whether the vaccine is protecting animals against challenge before post mortem examination. Finally we have been able to use the model to develop a vaccine that improves the efficacy of BCG against M. bovis challenge.
在过去几年里，由于牛结核病在英国等国家急剧增加，以及新西兰等国家野生动物宿主持续存在问题，对牛结核病的研究再度兴起。这项研究的目标之一是开发针对结核病的牛用疫苗。候选疫苗的初步测试在实验动物中进行，最初是小鼠，随后是豚鼠。牛疫苗接种计划的一个独特之处在于，在实验室模型中显示出前景的候选疫苗，在进入临床试验之前，可以在天然宿主物种牛身上进行测试。这比开发人类结核病疫苗的策略具有很大优势，在开发人类结核病疫苗时，当然不可能通过用病原体对宿主物种进行实验性攻击来测试候选疫苗。在牛身上测试候选疫苗最常用的模型是气管内接种10³至10⁴个牛分枝杆菌菌落形成单位。接种后观察到的病理变化与人类结核病相似，会引发明显的肉芽肿反应和主要的细胞免疫反应。利用这个模型，我们在牛结核病疫苗方面取得了一些重大进展。首先，我们开发了抗原混合物，当用于全血γ干扰素检测时，可以区分感染牛分枝杆菌的动物和接种卡介苗的动物。其次，我们开发了病理免疫相关指标，这使我们能够在尸检前评估疫苗是否能保护动物免受攻击。最后，我们能够利用这个模型开发一种疫苗，提高卡介苗对牛分枝杆菌攻击的效力。
