Lenz Nicole, Schindler Tobias, Kagina Benjamin M, Zhang Jitao David, Lukindo Tedson, Mpina Maxmillian, Bang Peter, Kromann Ingrid, Hoff Søren T, Andersen Peter, Reither Klaus, Churchyard Gavin J, Certa Ulrich, Daubenberger Claudia A
Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland Roche Pharmaceutical Research and Early Development, Department of Pharmaceutical Sciences/Translational Technologies and Bioinformatics, Roche Innovation Center Basel, Basel, Switzerland.
Clin Vaccine Immunol. 2015 Jul;22(7):688-96. doi: 10.1128/CVI.00092-15. Epub 2015 Apr 29.
Tuberculosis (TB) remains a global health problem, with vaccination being a necessary strategy for disease containment and elimination. A TB vaccine should be safe and immunogenic as well as efficacious in all affected populations, including HIV-infected individuals. We investigated the induction and maintenance of vaccine-induced memory CD4(+) T cells following vaccination with the subunit vaccine H1/IC31. H1/IC31 was inoculated twice on study days 0 and 56 among HIV-infected adults with CD4(+) lymphocyte counts of >350 cells/mm(3). Whole venous blood stimulation was conducted with the H1 protein, and memory CD4(+) T cells were analyzed using intracellular cytokine staining and polychromatic flow cytometry. We identified high responders, intermediate responders, and nonresponders based on detection of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) expressing central (TCM) and effector memory CD4(+) T cells (TEM) 182 days after the first immunization. Amplicon-based transcript quantification using next-generation sequencing was performed to identify differentially expressed genes that correlated with vaccine-induced immune responses. Genes implicated in resolution of inflammation discriminated the responders from the nonresponders 3 days after the first inoculation. The volunteers with higher expression levels of genes involved in antiviral innate immunity at baseline showed impaired H1-specific TCM and TEM maintenance 6 months after vaccination. Our study showed that in HIV-infected volunteers, expression levels of genes involved in the antiviral innate immune response affected long-term maintenance of H1/IC31 vaccine-induced cellular immunity. (The clinical trial was registered in the Pan African Clinical Trials Registry [PACTR] with the identifier PACTR201105000289276.).
结核病（TB）仍然是一个全球性的健康问题，疫苗接种是控制和消除该疾病的必要策略。一种结核病疫苗应具备安全性、免疫原性，并且在所有受影响人群中都有效，包括艾滋病毒感染者。我们研究了亚单位疫苗H1/IC31接种后疫苗诱导的记忆性CD4(+) T细胞的诱导和维持情况。在第0天和第56天对CD4(+)淋巴细胞计数>350个细胞/mm(3)的艾滋病毒感染成年人进行了两次H1/IC31接种。用H1蛋白进行全静脉血刺激，并使用细胞内细胞因子染色和多色流式细胞术分析记忆性CD4(+) T细胞。在首次免疫后182天，根据白细胞介素-2（IL-2）、肿瘤坏死因子α（TNF-α）和γ干扰素（IFN-γ）表达的中枢性（TCM）和效应性记忆CD4(+) T细胞（TEM）的检测，我们确定了高反应者、中度反应者和无反应者。使用下一代测序进行基于扩增子的转录本定量，以鉴定与疫苗诱导的免疫反应相关的差异表达基因。在首次接种后3天，参与炎症消退的基因将反应者与无反应者区分开来。在基线时具有较高抗病毒先天免疫相关基因表达水平的志愿者在接种疫苗6个月后显示H1特异性TCM和TEM维持受损。我们的研究表明，在艾滋病毒感染的志愿者中，参与抗病毒先天免疫反应的基因表达水平影响H1/IC31疫苗诱导的细胞免疫的长期维持。（该临床试验已在泛非临床试验注册中心[PACTR]注册，标识符为PACTR201105000289276。）
