Chirkova T V, Naykhin A N, Petukhova G D, Korenkov D A, Donina S A, Mironov A N, Rudenko L G
Department of Virology, Institute of Experimental Medicine, Acad. Pavlov St. 12, Saint Petersburg 197376, Russia.
Clin Vaccine Immunol. 2011 Oct;18(10):1710-8. doi: 10.1128/CVI.05116-11. Epub 2011 Aug 3.
Cellular immune responses of both CD4 and CD8 memory/effector T cells were evaluated in healthy young adults who received two doses of live attenuated influenza A (H5N2) vaccine. The vaccine was developed by reassortment of nonpathogenic avian A/Duck/Potsdam/1402-6/68 (H5N2) and cold-adapted A/Leningrad/134/17/57 (H2N2) viruses. T-cell responses were measured by standard methods of intracellular cytokine staining of gamma interferon (IFN-γ)-producing cells and a novel T-cell recognition of antigen-presenting cells by protein capture (TRAP) assay based on the trogocytosis phenomenon, namely, plasma membrane exchange between interacting immune cells. TRAP enables the detection of activated trogocytosis-positive T cells after virus stimulation. We showed that two doses of live attenuated influenza A (H5N2) vaccine promoted both CD4 and CD8 T-memory-cell responses in peripheral blood of healthy young subjects in the clinical study. Significant differences in geometric mean titers (GMTs) of influenza A (H5N2)-specific IFN-γ(+) cells were observed at day 42 following the second vaccination, while peak levels of trogocytosis(+) T cells were detected earlier, on the 21st day after the second vaccination. The inverse correlation of baseline levels compared to postvaccine fold changes in GMTs of influenza-specific CD4 and CD8 T cells demonstrated that baseline levels of these specific cells could be considered a predictive factor of vaccine immunogenicity.
在接种两剂甲型流感（H5N2）减毒活疫苗的健康年轻成年人中评估了CD4和CD8记忆/效应T细胞的细胞免疫反应。该疫苗是通过将非致病性禽源A/鸭/波茨坦/1402-6/68（H5N2）病毒与冷适应的A/列宁格勒/134/17/57（H2N2）病毒重配而研发的。通过检测产生γ干扰素（IFN-γ）细胞的细胞内细胞因子染色的标准方法以及基于胞啃现象（即相互作用的免疫细胞之间的质膜交换）的蛋白质捕获（TRAP）测定法来测量T细胞反应，TRAP可检测病毒刺激后活化的胞啃阳性T细胞。我们发现在临床研究中，两剂甲型流感（H5N2）减毒活疫苗促进了健康年轻受试者外周血中CD4和CD8 T记忆细胞反应。在第二次接种后第42天观察到甲型流感（H5N2）特异性IFN-γ(+)细胞的几何平均滴度（GMT）有显著差异，而胞啃(+) T细胞的峰值水平在第二次接种后第21天更早被检测到。与流感特异性CD4和CD8 T细胞的疫苗后GMT倍数变化相比，基线水平呈负相关，这表明这些特异性细胞的基线水平可被视为疫苗免疫原性的预测因素。
