Infections with varicella zoster virus (VZV), a member of the Herpesviridae family, are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox, and due to the virus capacity to remain latent in neurons, it can reactivate later in life causing herpes zoster (HZ), also known as shingles. Two different vaccines have been developed to prevent HZ, one based on a live attenuated VZV strain (Zostavax) and the other on adjuvanted gE recombinant protein (Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (80 years of age and beyond). In this context, it is of much interest to understand if there is a role for T cell immunity in differential clinical outcome, and if there is a correlate of protection between T cell immunity and Shingrix efficacy. In this study, we characterized Shingrix specific ex vivo CD4 T cell responses in the context of natural exposure and HZ vaccination using pools of predicted epitopes. We show that T cell reactivity following natural infection and Zostavax vaccination dominantly targets non-structural proteins (NS), while Shingrix vaccination redirects dominant reactivity to target gE. We mapped the gE-specific responses following Shingrix vaccination to 89 different gE epitopes, 34 of which accounted for 80% of the response. Using antigen presentation assays and single HLA molecule transfected lines, we experimentally determined HLA restrictions for 94 different donor/peptide combinations. Finally, we used our results as a training set to assess strategies to predict restrictions based on measured or predicted HLA binding and the corresponding HLA types of responding subjects.

中文翻译：

---

Shingrix疫苗接种后CD4 + T细胞表位的鉴定和表征。

水痘带状疱疹病毒（VZV）（疱疹病毒科成员）的感染与一系列临床表现有关。VZV的初次感染会导致水痘，并且由于病毒在神经元中保持潜伏的能力，它可以在以后的生命中重新激活，从而导致带状疱疹（HZ），也称为带状疱疹。已经开发出两种预防HZ的疫苗，一种基于减毒活VZV株（Zostavax），另一种基于佐剂gE重组蛋白（Shingrix）。尽管Zostavax的功效随着年龄的增长而减弱，但Shingrix的保护作用在老年受试者（80岁及以上）中仍保持其效力。在这种情况下，了解T细胞免疫是否在不同的临床结果中发挥作用以及T细胞免疫与Shingrix功效之间是否存在保护相关性非常重要。在这项研究中，我们表征了Shingrix特异性离体CD4 T细胞反应的自然暴露和HZ疫苗接种中使用的预测表位池。我们显示自然感染和Zostavax疫苗接种后的T细胞反应性主要针对非结构蛋白（NS），而Shingrix疫苗接种则将主要反应性重定向至目标gE。我们将Shingrix疫苗接种后的gE特异性反应映射到89个不同的gE表位，其中34个占表位的80％。使用抗原呈递分析和单个HLA分子转染的品系，我们通过实验确定了94种不同供体/肽组合的HLA限制。最后，