Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis
Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis
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DOI：
10.1073/pnas.0703510104
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发表时间：
2007-07-24
影响因子：
11.1
通讯作者：
Kaufmann, Stefan H. E.
中科院分区：
文献类型：
--
作者：
Mittruecker, Hans-Willi;Steinhoff, Ulrich;Kaufmann, Stefan H. E.
卡介苗（Mycobacterium bovis bacille Calmette-Guerin，BCG）是目前应用最广泛的活菌疫苗。然而，有限的信息是可用的相关途径和剂量的疫苗接种和诱导特异性T细胞反应与保护免受结核病。我们比较了口服和全身接种疫苗的效果，以及疫苗诱导的T细胞应答与小鼠实验性结核病的保护作用。在口服和全身接种后，我们观察到BCG的持久性和传播以及特异性IFN-γ分泌性CD 4（+）和CD 8（+）T细胞的频率和位置存在显著差异。然而，两种接种途径对结核分枝杆菌气溶胶攻击的保护水平相当。保护与特异性CD 8 + T细胞在受攻击小鼠的感染组织中的快速积累最相关。相反，CD 4（+）T细胞产生的特异性IFN-γ反映了M的负荷。结核病而不是保护的力量。我们的数据对CD 4（+）T细胞分泌IFN-γ的测量提出了质疑，并强调需要新的生物标志物来评估结核疫苗的效力。
Mycobacterium bovis bacille Calmette-Guerin (BCG) is the most widely used live bacterial vaccine. However, limited information is available correlating route and dose of vaccination and induction of specific T cell responses with protection against tuberculosis. We compared efficacy of oral and systemic vaccination and correlated vaccine-induced T cell responses with protection in experimental tuberculosis of mice. After oral and systemic vaccination, we observed profound differences in persistence and dissemination of BCG and frequencies and location of specific IFN-gamma-secreting CD4(+) and CD8(+) T cells. Yet, both vaccination routes caused comparable levels of protection against aerosol challenge with Mycobacterium tuberculosis. Protection correlated best with rapid accumulation of specific CD8+ T cells in infected tissues of challenged mice. In contrast, specific IFN-gamma production by CD4(+) T cells reflected the load of M. tuberculosis rather than the strength of protection. Our data question the measurement of IFN-gamma secretion by CD4(+) T cells and emphasize the need for new biomarkers for evaluation of tuberculosis vaccine efficacies.