Department of Immunology, Max Planck Institute for Infection Biology, Berlin.
J Infect Dis. 2011 Nov 15;204(10):1573-84. doi: 10.1093/infdis/jir592. Epub 2011 Sep 20.
New vaccines against tuberculosis (TB) are urgently needed because the only available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), fails to protect against pulmonary TB in adults. The recombinant ΔureC hly+ BCG (rBCG) is more efficient than parental BCG (pBCG) against pulmonary TB in preclinical studies and has proven safe and immunogenic in phase I clinical trials.
In an attempt to identify the mechanisms underlying the superior protection of rBCG, we compared the immune responses elicited after vaccination and subsequent aerosol infection with Mycobacterium tuberculosis (MTB) in mice.
We demonstrate that both rBCG and pBCG induce marked type 1 cytokine responses, whereas only rBCG elicits a profound type 17 cytokine response in addition. We observed earlier recruitment of antigen-specific T lymphocytes to the lung upon MTB infection of rBCG-vaccinated mice. These T cells produced abundant type 1 cytokines after restimulation, resulting in 10-fold reduced bacterial burden 90 days after infection.
Our findings identify a general immunologic pathway for improved vaccination strategies against TB that can also be harnessed by other vaccine candidates.
由于唯一可用的疫苗卡介苗（BCG）不能预防成人肺结核，因此迫切需要新的结核病疫苗。与亲本 BCG（pBCG）相比，重组 ΔureC hly+ BCG（rBCG）在临床前研究中对肺结核的防治效果更好，并且在 I 期临床试验中已被证明是安全和免疫原性的。
为了确定 rBCG 优越保护作用的机制，我们比较了接种疫苗后和随后用结核分枝杆菌（MTB）气溶胶感染小鼠引起的免疫反应。
我们证明 rBCG 和 pBCG 都能诱导强烈的 1 型细胞因子反应，而 rBCG 还能诱导深刻的 17 型细胞因子反应。我们观察到 rBCG 接种的小鼠在 MTB 感染后，抗原特异性 T 淋巴细胞更早地募集到肺部。这些 T 细胞在再刺激后产生大量的 1 型细胞因子，导致感染后 90 天细菌负荷减少 10 倍。
我们的研究结果确定了一种针对结核病的改进疫苗接种策略的一般免疫途径，其他疫苗候选物也可以利用这种途径。
