Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, USA.
Vaccine. 2011 Nov 21;29(50):9308-15. doi: 10.1016/j.vaccine.2011.10.019. Epub 2011 Oct 18.
The hallmark of a vaccine is to induce long-term protective immunity against the pathogen. The use of Mycobacterium bovis BCG as a vaccine against tuberculosis has been problematic in that immunity induced by BCG wanes over time and it may be less effective against more virulent strains of Mycobacterium tuberculosis. Thus it is important to determine what factors might be associated with waning or inefficient immunity. One such factor has been associated with the difference in many types of BCG that are used around the world, or more specifically due to the loss of genomic material in the various sub-strains used in vaccination programs. To address this issue we investigated the long-term immune response generated by 3 sub-strains BCG in the C57BL/6 mouse model of experimental tuberculosis. Mice vaccinated with these diverse strains of BCG were assessed at 6 and 12 months post-vaccination. All BCG sub-strain induced elevated levels of IFN-γ-producing cells at each time point as determined by ELISpot assay. However, when mice were challenged at 6 and 12 months with either M. tuberculosis H37Rv or HN878 the ability of the BCG sub-strains to protect vaccinated mice varied, depending on the time of challenge and on the strain used to infect mice. BCG Pasteur was then used to vaccinate guinea pigs, which were subsequently infected with either H37Rv or HN878. Data showed that BCG Pasteur prolonged the survival of guinea pigs against infection with both strains. Taken together these data suggest that longevity of the immune response generated by BCG is not related to the loss of genetic material and that BCG can induce a protective immune response to infection with a clinical strain of M. tuberculosis.
疫苗的标志是诱导针对病原体的长期保护性免疫。使用牛分枝杆菌 BCG 作为结核病疫苗存在问题，因为 BCG 诱导的免疫随着时间的推移而减弱，并且它可能对更具毒力的结核分枝杆菌菌株的效果较差。因此，确定哪些因素可能与免疫减弱或无效有关非常重要。一个这样的因素与世界各地使用的许多类型的 BCG 之间的差异有关，或者更具体地说，由于在疫苗接种计划中使用的各种亚株中基因组物质的丢失。为了解决这个问题，我们研究了 3 种 BCG 亚株在实验性结核分枝杆菌感染的 C57BL/6 小鼠模型中产生的长期免疫反应。用这些不同的 BCG 亚株接种疫苗的小鼠在接种后 6 个月和 12 个月进行评估。通过 ELISpot 测定，所有 BCG 亚株在每个时间点均诱导产生高水平的 IFN-γ产生细胞。然而，当小鼠在 6 个月和 12 个月时分别用结核分枝杆菌 H37Rv 或 HN878 进行攻毒时，BCG 亚株保护接种小鼠的能力因攻毒时间和感染小鼠的菌株而异。然后用 BCG Pasteur 对豚鼠进行疫苗接种，随后用 H37Rv 或 HN878 感染这些豚鼠。数据表明 BCG Pasteur 延长了豚鼠对两种菌株感染的存活时间。综上所述，这些数据表明，BCG 产生的免疫反应的持久性与遗传物质的丢失无关，并且 BCG 可以诱导针对结核分枝杆菌临床株感染的保护性免疫反应。
