用重组流感 A 病毒结核疫苗增强卡介苗可增加肺部 T 细胞反应,但不能预防结核分枝杆菌感染。
Boosting BCG with recombinant influenza A virus tuberculosis vaccines increases pulmonary T cell responses but not protection against Mycobacterium tuberculosis infection.
机构信息
Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.
School of Medicine, Deakin University, Geelong, Victoria, Australia.
出版信息
PLoS One. 2021 Nov 18;16(11):e0259829. doi: 10.1371/journal.pone.0259829. eCollection 2021.
The current Mycobacterium bovis BCG vaccine provides inconsistent protection against pulmonary infection with Mycobacterium tuberculosis. Immunity induced by subcutaneous immunization with BCG wanes and does not promote early recruitment of T cell to the lungs after M. tuberculosis infection. Delivery of Tuberculosis (TB) vaccines to the lungs may increase and prolong immunity at the primary site of M. tuberculosis infection. Pulmonary immunization with recombinant influenza A viruses (rIAVs) expressing an immune-dominant M. tuberculosis CD4+ T cell epitope (PR8-p25 and X31-p25) stimulates protective immunity against lung TB infection. Here, we investigated the potential use of rIAVs to improve the efficacy of BCG using simultaneous immunization (SIM) and prime-boost strategies. SIM with parenteral BCG and intranasal PR8-p25 resulted in equivalent protection to BCG alone against early, acute and chronic M. tuberculosis infection. Boosting BCG with rIAVs increased the frequency of IFN-γ-secreting specific T cells (p<0.001) and polyfunctional CD4+ T cells (p<0.05) in the lungs compared to the BCG alone, however, this did not result in a significant increase in protection against M. tuberculosis compared to BCG alone. Therefore, sequential pulmonary immunization with these rIAVs after BCG increased M. tuberculosis-specific memory T cell responses in the lung, but not protection against M. tuberculosis infection.
当前的牛分枝杆菌卡介苗(BCG)疫苗对结核分枝杆菌(Mycobacterium tuberculosis)引起的肺部感染提供的保护作用并不一致。通过皮下接种 BCG 诱导的免疫会逐渐减弱,并且在结核分枝杆菌感染后不会促进 T 细胞早期募集到肺部。将结核疫苗(TB)递送至肺部可能会增加和延长结核分枝杆菌感染的主要部位的免疫。用表达免疫显性结核分枝杆菌 CD4+ T 细胞表位(PR8-p25 和 X31-p25)的重组甲型流感病毒(rIAV)对肺部进行免疫接种可刺激针对肺部结核感染的保护性免疫。在这里,我们研究了使用同时免疫(SIM)和初免-加强策略利用 rIAV 来提高 BCG 疗效的潜力。用 rIAV 对 BCG 进行同时免疫和鼻腔内接种 PR8-p25 与单独使用 BCG 相比,对早期、急性和慢性结核分枝杆菌感染具有等效的保护作用。与单独使用 BCG 相比,用 rIAV 加强 BCG 可增加肺部中 IFN-γ 分泌的特异性 T 细胞(p<0.001)和多功能 CD4+ T 细胞(p<0.05)的频率,但这并没有导致对结核分枝杆菌的保护作用明显增加与单独使用 BCG 相比。因此,在接种 BCG 后,用这些 rIAV 序贯对肺部进行免疫接种可增加肺部中结核分枝杆菌特异性记忆 T 细胞反应,但不能预防结核分枝杆菌感染。