Improving vaccines against tuberculosis
Improving vaccines against tuberculosis
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DOI：
10.1046/j.0818-9641.2002.01143.x
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发表时间：
2003-02-01
影响因子：
4
通讯作者：
Palendira, U
中科院分区：
文献类型：
--
作者：
Britton, WJ;Palendira, U
结核病仍然是全世界死亡以及身体和经济匮乏的主要原因。最近，我们对结核分枝杆菌基因组、分枝杆菌遗传学和保护性免疫的宿主决定因素的理解取得了重大进展。然而，挑战在于如何利用这些信息来开发比卡介苗更有效的疫苗，卡介苗是卡介苗和盖林在近 90 年前衍生出的牛分枝杆菌减毒株。卡介苗的一些局限性包括保护性免疫力随着时间的推移而减弱、与播散性疾病相比对肺结核的有效性降低以及活疫苗在免疫功能低下受试者中的问题。目前正在寻求两种广泛的疫苗开发方法。新的活疫苗包括通过随机诱变或定向删除假定的毒力因子产生的减毒结核分枝杆菌菌株，或者通过卡介苗的基因操作来表达新的抗原或细胞因子。第二种方法利用非活性亚单位疫苗来递送免疫显性分枝杆菌抗原。蛋白质疫苗和 DNA 疫苗均可对小鼠实验性结核感染产生部分保护，但其功效通常相当于或低于卡介苗。将讨论细胞因子佐剂和针对抗原呈递细胞的疫苗在增强保护方面的比较效果。使用质粒白细胞介素 12 和表达抗原 85B（一种主要分泌蛋白）的 DNA 疫苗进行联合免疫，具有与卡介苗一样的保护作用。 DNA-85B 引发和 BCG 加强的组合优于单独使用 BCG。因此，与卡介苗相比，有可能实现更高水平的结核病保护，这凸显了新型结核病疫苗在人类中的潜力。
Tuberculosis remains a major cause of mortality and physical and economic deprivation worldwide. There have been significant recent advances in our understanding of the Mycobacterium tuberculosis genome, mycobacterial genetics and the host determinants of protective immunity. Nevertheless, the challenge is to harness this information to develop a more effective vaccine than BCG, the attenuated strain of Mycobacterium bovis derived by Calmette and Guerin nearly 90 years ago. Some of the limitations of BCG include the waning of the protective immunity with time, reduced effectiveness against pulmonary tuberculosis compared to disseminated disease, and the problems of a live vaccine in immuno-compromised subjects. Two broad approaches to vaccine development are being pursued. New live vaccines include either attenuated strains of Mycobacterium tuberculosis produced by random mutagenesis or targeted deletion of putative virulence factors, or by genetic manipulation of BCG to express new antigens or cytokines. The second approach utilizes non-viable subunit vaccines to deliver immunodominant mycobacterial antigens. Both protein and DNA vaccines induce partial protection against experimental tuberculosis infection in mice, however, their efficacy has generally been equivalent to or less than that of BCG. The comparative effects of cytokine adjuvants and vaccines targeting antigen presenting cells on enhancing protection will be discussed. Coimmunization with plasmid interleukin-12 and a DNA vaccine expressing Antigen 85B, a major secreted protein, was as protective as BCG. The combination of priming with DNA-85B and boosting with BCG was superior to BCG alone. Therefore it is possible to achieve a greater level of protection against tuberculosis than with BCG, and this highlights the potential for new tuberculosis vaccines in humans.