Human T-cell responses to vaccinia virus envelope proteins.
Human T-cell responses to vaccinia virus envelope proteins.
复制标题
人类 T 细胞对痘苗病毒包膜蛋白的反应。
DOI：
10.1128/jvi.00601-06
复制
发表时间：
2006
影响因子：
5.4
通讯作者：
Flomenberg,Phyllis
中科院分区：
文献类型：
--
作者：
Tang,Jie;Murtadha,Mariam;Schnell,Matthias;Eisenlohr,LaurenceC;Hooper,Jay;Flomenberg,Phyllis
更安全的天花疫苗的一种方法是利用重组亚基而不是活痘苗病毒（VACV）。 VACV 包膜基因 A27L、L1R、B5R 和 A33R 的产物在动物模型中诱导保护性抗体。我们认为，引发 T 细胞反应的蛋白质以及中和抗体对于分子疫苗来说非常重要。为了评估 VACV 特异性记忆 T 细胞反应，使用 γ 干扰素酶联免疫斑点和细胞因子流式细胞术测定，对来自 4 名 VACV 疫苗接种者的外周血单核细胞 (PBMC) 进行了针对整个 VACV 和单个包膜蛋白 A27、B5、L1 和 A33 的测试。用感染 VACV 的自体树突状细胞刺激 PBMC，或用单独的 VACV 蛋白 mRNA 电穿孔。来自所有捐赠者的 T 细胞系，从 1 个月到 20 多年前接种过疫苗，都能识别所有四种 VACV 包膜蛋白。检测到 CD4+ 和 CD8+T 细胞对每种蛋白质的反应。进一步分析集中于代表性蛋白质 B5 和 A27。最近接种疫苗的人的 PBMC 表现出高频率的 B5（分别为 19.8% 和 20%）和 A27（6.8% 和 3.7%）的 CD4+ 和 CD8+ T 细胞前体。相比之下，3 年前接种疫苗的捐赠者中，B5 和 A27 特异性 T 细胞频率范围为 0.4% 至 1.3%。使用重叠的 15 聚体肽从 A27 和 B5 中鉴定出多个 CD4+ 和 CD8+ T 细胞表位。这些数据表明，所有四种 VACV 包膜蛋白可能有助于保护性免疫，不仅通过诱导抗体反应，而且还通过引发 T 细胞反应。
One approach for a safer smallpox vaccine is to utilize recombinant subunits rather than live vaccinia virus (VACV). The products of the VACV envelope genes A27L, L1R, B5R, and A33R induce protective antibodies in animal models. We propose that proteins that elicit T-cell responses, as well as neutralizing antibodies, will be important to include in a molecular vaccine. To evaluate VACV-specific memory T-cell responses, peripheral blood mononuclear cells (PBMC) from four VACV vaccinees were tested against whole VACV and the individual envelope proteins A27, B5, L1, and A33, using gamma interferon enzyme-linked immunospot and cytokine flow cytometry assays. PBMC were stimulated with autologous dendritic cells infected with VACV or electroporated with individual VACV protein mRNAs. T-cell lines from all donors, vaccinated from 1 month to over 20 years ago, recognized all four VACV envelope proteins. Both CD4+and CD8+T-cell responses to each protein were detected. Further analysis focused on representative proteins B5 and A27. PBMC from a recent vaccinee exhibited high frequencies of CD4+and CD8+T-cell precursors to both B5 (19.8 and 20%, respectively) and A27 (6.8 and 3.7%). In comparison, B5- and A27-specific T-cell frequencies ranged from 0.4 to 1.3% in a donor vaccinated 3 years ago. Multiple CD4+and CD8+T-cell epitopes were identified from both A27 and B5, using overlapping 15-mer peptides. These data suggest that all four VACV envelope proteins may contribute to protective immunity, not only by inducing antibody responses, but also by eliciting T-cell responses.