Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore
Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore
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DOI：
10.4161/hv.25562
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发表时间：
2013-11-01
影响因子：
4.8
通讯作者：
Guy, Bruno
中科院分区：
文献类型：
--
作者：
Harenberg, Anke;Begue, Sarah;Guy, Bruno
为了表征研究中的 CYD 四价登革热疫苗 (TDV) 诱导的细胞介导免疫 (CMI)，我们开发了全血、细胞内细胞因子染色 (ICS) 测定和多重测定，每种测定需要 3 mL 血液。我们对参加新加坡一项 II 期试验（ClinicalTrial.gov NCT NCT00880893）的 80 名青少年和成人子集进行了第一次和第三次注射 CYD-TDV 之前、之后 28 天以及第三次注射后一年的 CMI 评估。在接种疫苗之前检测到针对登革热 NS3 的 CD4/IFN γ/TNF α 特异性反应。疫苗接种在所有参与者中诱导 YF-17D-NS3 特异性 CD8/IFN γ 反应，但没有显着的 TNF α 和 CYD 特异性 Th1/Tc1 细胞反应，其特征是与 TNF α 相比，IFN γ 分泌占主导地位，与每种 CYD 疫苗病毒再刺激后外周血单核细胞 (PBMC) 上清液多重分析中的低水平 IL-13 分泌相关。第一次疫苗接种后，反应主要针对 CYD-4，第三次疫苗接种后，针对所有四种血清型的反应更加平衡。第三次疫苗接种一年后观察到相同的定性特征，NS3 特异性反应降低约 2 倍，血清型特异性细胞反应降低 3 倍。这些发现证实了先前关于 CYD-TDV 诱导的细胞反应的性质和特异性的观察结果，并首次证明了一年后细胞反应的持续性。我们还建立了用小量血液样本分析 CMI 的可行性，使得此类分析可以考虑用于儿科试验。
To characterize the cell mediated immunity (CMI) induced by the investigational CYD tetravalent dengue vaccine (TDV), we developed a whole-blood, intracellular cytokine staining (ICS) assay and a multiplex assay, each requiring 3 mL of blood. We assessed CMI before and 28 d after a first and third injection of CYD-TDV and one year after the third injection in a subset of 80 adolescents and adults enrolled in a phase II trial in Singapore (ClinicalTrial.gov NCT NCT00880893). CD4/IFN gamma/TNF alpha responses specific to dengue NS3 were detected before vaccination. Vaccination induced YF-17D-NS3-specific CD8/IFN gamma responses, without significant TNF alpha, and a CYD-specific Th1/Tc1 cellular response in all participants, which was characterized by predominant IFN gamma secretion compared with TNF alpha, associated with low level IL-13 secretion in multiplex analysis of peripheral blood mononuclear cells (PBMC) supernatants after restimulation with each the CYD vaccine viruses. Responses were directed mainly against CYD-4 after the first vaccination, and were more balanced against all four serotypes after the third vaccination. The same qualitative profile was observed one year after the third vaccination, with approximately 2-fold lower NS3-specific responses, and 3-fold lower serotype-specific cellular responses. These findings confirm previous observations regarding both the nature and specificity of cellular responses induced by CYD-TDV, and for the first time demonstrate the persistence of cellular responses after one year. We also established the feasibility of analyzing CMI with small blood samples, allowing such analysis to be considered for pediatric trials.