用重组腺病毒疫苗对小鼠进行免疫接种，可抑制感染后结核分枝杆菌的早期生长。

BACKGROUND

In pulmonary Mycobacterium tuberculosis (Mtb) infection, immune responses are delayed compared to other respiratory infections, so that antigen-specific cells are not detected in the lungs earlier than day 14. Even after parenteral immunization with Bacille Calmette Guerin (BCG) or a subunit vaccine, the immune response after Mtb challenge is only slightly accelerated and the kinetics of pulmonary Mtb growth do not differ between naïve and immunized animals up to day 14.

METHODS AND FINDINGS

Mice were immunized intranasally with a recombinant adenovirus expressing mycobacterial antigen 85A (Ad85A), challenged by aerosol with Mtb and the kinetics of Mtb growth in the lungs measured. Intranasal immunization with Ad85A inhibits Mtb growth in the early phase of infection, up to day 8. Protection is sustained for at least 7 months and correlates with the presence of antigen-specific activated effector CD8 T cells in the lungs. Antigen 85A-specific T cells respond to antigen presenting cells from the lungs of mice immunized with Ad85A 23 weeks previously, demonstrating the persistence of antigen in the lungs.

CONCLUSIONS/SIGNIFICANCE: Intranasal immunization with Ad85A can inhibit early growth of Mtb because it establishes a lung antigen depot and maintains an activated lung-resident lymphocyte population. We propose that an optimal immunization strategy for tuberculosis should aim to induce both lung and systemic immunity, targeting the early and late phases of Mtb growth.

背景

在肺部结核分枝杆菌（Mtb）感染中，免疫反应比其他呼吸道感染延迟，因此在第 14 天之前不会在肺部更早地检测到抗原特异性细胞。即使在接种卡介苗（BCG）或亚单位疫苗后进行了皮内免疫，Mtb 挑战后的免疫反应也只是略微加速，并且在第 14 天之前，未免疫和免疫动物的肺部 Mtb 生长动力学没有差异。

方法和发现

用表达分枝杆菌抗原 85A 的重组腺病毒（Ad85A）经鼻内免疫小鼠，用 Mtb 气溶胶进行挑战，并测量肺部 Mtb 生长的动力学。鼻内免疫 Ad85A 可抑制感染早期的 Mtb 生长，直至第 8 天。保护作用可持续至少 7 个月，并与肺部存在抗原特异性激活效应 CD8 T 细胞相关。抗原 85A 特异性 T 细胞可响应来自 Ad85A 免疫小鼠肺部的抗原呈递细胞，证明抗原在肺部的持续存在。

结论/意义：用 Ad85A 经鼻内免疫可抑制 Mtb 的早期生长，因为它建立了肺部抗原储存库并维持了激活的肺部驻留淋巴细胞群体。我们提出，结核病的最佳免疫策略应旨在诱导肺部和全身免疫，针对 Mtb 生长的早期和晚期。