Use of the bovine model of tuberculosis for the development of improved vaccines and diagnostics
Use of the bovine model of tuberculosis for the development of improved vaccines and diagnostics
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DOI：
10.1016/s1472-9792(02)00062-8
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发表时间：
2003-01-01
期刊：
影响因子：
3.2
通讯作者：
Buddle, BM
中科院分区：
文献类型：
--
作者：
Hewinson, RG;Vordermeier, HM;Buddle, BM
在过去的几年里，由于牛结核病在英国等国的急剧上升，以及新西兰等国野生动物水库的持续问题，对牛结核病的研究重新兴起。这项研究的目标之一是开发针对结核病的牛疫苗。候选疫苗的初步测试是在实验室动物身上进行的，最初是小鼠，随后是豚鼠。牛只疫苗接种计划的一个独特特点是，在实验室模型中显示出希望的候选疫苗随后可以在自然宿主物种牛身上进行测试，然后进行临床试验。与开发人类结核病疫苗的策略相比，这是一个重大优势。当然，在人类结核病疫苗开发策略中，不可能通过用病原体对宿主物种进行实验来测试候选疫苗。在牛身上测试候选疫苗最常用的模型是在气管内挑战103到104个形成牛分枝杆菌菌落的单位。挑战后观察到的病理类似于人类结核病，引起明显的肉芽肿反应和主要的细胞免疫反应。使用这个模型，我们已经能够在牛结核病疫苗方面取得一些重大进展。首先，我们已经开发出了抗原鸡尾酒，当用于全血干扰素检测时，可以区分感染牛瘟和接种卡介苗的动物。接下来，我们开发了与病理学相关的免疫因素，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，我们已经能够使用该模型来开发一种疫苗，该疫苗可以提高卡介苗对抗牛分枝杆菌攻击的效力。皇冠版权所有(C)2003由爱思唯尔科学有限公司出版。保留所有权利。
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 103 and 104 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 A 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. Crown Copyright (C) 2003 Published by Elsevier Science Ltd. All rights reserved.