Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the zoster vaccine live (ZVL), which provided limited and short-lived protection, has been supplanted by the superior recombinant zoster vaccine (RZV), which provides robust and durable protection. To understand the mechanisms underlying the differential immunologic characteristics of the 2 vaccines, we used T cell receptor β chain sequencing and peptide-MHC class II tetramer staining to analyze recombinant glycoprotein E-specific (gE-specific) CD4+ T cell clonotypes in RZV and ZVL recipients. Compared with ZVL, RZV expanded more gE-specific CD4+ clonotypes, with greater breadth and higher frequency of public clonotypes. RZV recruited a higher proportion of clonotypes from naive than from memory cells, while ZVL recruited equally from memory and naive compartments. Compared with memory-derived, naive-derived clonotypes were more likely to last 5 or more years after immunization. Moreover, the frequency of tetramer+ persistent clones correlated with the frequency of tetramer+ naive CD4+ prevaccination T cells. We conclude that the ability of RZV to recruit naive CD4+ T cells into the response may contribute to the durability of its effect. The abundance, breadth, and frequency of public clonotypes may further add to its protective effect.

中文翻译：

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重组带状疱疹疫苗招募初始 CD4+ T 细胞与持续免疫相关。


带状疱疹 (HZ) 对于细胞介导免疫力下降的人（包括老年人）来说是一个严重的问题。带状疱疹活疫苗 (ZVL) 是第一种被批准用于预防带状疱疹的疫苗，它提供有限且短暂的保护，现已被卓越的重组带状疱疹疫苗 (RZV) 取代，后者提供强大而持久的保护。为了了解两种疫苗差异免疫学特征的机制，我们使用 T 细胞受体 β 链测序和肽-MHC II 类四聚体染色来分析 RZV 和 ZVL 中的重组糖蛋白 E 特异性（gE 特异性）CD4+ T 细胞克隆型收件人。与ZVL相比，RZV扩增了更多的gE特异性CD4+克隆型，公共克隆型的广度和频率更高。 RZV 从幼稚细胞中募集的克隆型比例高于从记忆细胞中募集的克隆型比例，而 ZVL 从记忆细胞和幼稚细胞中募集的克隆型比例相同。与记忆衍生的克隆型相比，幼稚衍生的克隆型更有可能在免疫后持续 5 年或更长时间。此外，四聚体+持久性克隆的频率与四聚体+初始CD4+预接种T细胞的频率相关。我们得出的结论是，RZV 招募初始 CD4+ T 细胞参与反应的能力可能有助于其效果的持久性。公共克隆型的丰富性、广度和频率可能进一步增强其保护作用。