Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus
Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus
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DOI：
10.1093/infdis/jiv164
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发表时间：
2015-10-01
影响因子：
6.4
通讯作者：
Koelle, David M.
中科院分区：
文献类型：
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作者：
Laing, Kerry J.;Russell, Ronnie M.;Koelle, David M.
背景。活的减毒水痘疫苗株 (vOka) 是唯一获得许可的治疗性疫苗。水痘带状疱疹病毒（VZV）特异性细胞免疫的增强是一种可能的作用机制。我们检查了基线时和带状疱疹疫苗接种后记忆 CD4(+) T 细胞对每种 VZV 蛋白的反应。方法。从 12 名接种 Zostavax 的受试者中采集连续血样，并通过离体 VZV 特异性 T 细胞和抗体测定证实免疫原性。生成富含 VZV 特异性的 CD4(+) T 细胞系，并探测其对每种 VZV 蛋白和选定肽组的增殖反应。结果。带状疱疹疫苗接种后 1 个月，VZV 特异性 CD4(+) T 细胞的中位数（2.3 倍）和广度（4.2 倍）增加。两项指标均下降了 6 个月。基线时最常见的反应包括 VZV 开放阅读框 (ORF) 68、4、37 和 63。接种疫苗后，对 ORF 40、67、9、59、12、62 和 18 的反应也很普遍。使用肽证实了ORF9和ORF18的免疫原性，定义了大量离散的CD4(+)T细胞表位。结论。带状疱疹疫苗接种后，VZV 特异性 CD4(+) T 细胞反应的广度和强度都会增加。除了糖蛋白 E (ORF68) 之外，我们还鉴定了可能是亚单位疫苗有用成分的抗原 ORF。
Background. The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of varicella zoster virus (VZV)-specific cellular immunity is a likely mechanism of action. We examined memory CD4(+) T-cell responses to each VZV protein at baseline and after zoster vaccination.Methods. Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-cell and antibody assays. CD4(+) T-cell lines enriched for VZV specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets.Results. Zoster vaccination increased the median magnitude (2.3-fold) and breadth (4.2-fold) of VZV-specific CD4(+) T cells one month post-vaccination. Both measures declined by 6 months. The most prevalent responses at baseline included VZV open reading frames (ORFs) 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete CD4(+) T-cell epitopes.Conclusions. The breadth and magnitude of the VZV-specific CD4(+) T-cell response increase after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines.