Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.
Division of Allergy and Infectious Diseases, Department of Medicine, and.
JCI Insight. 2024 Jun 18;9(14):e179010. doi: 10.1172/jci.insight.179010.
The skin at the site of HSV-2 reactivation is enriched for HSV-2-specific T cells. To evaluate whether an immunotherapeutic vaccine could elicit skin-based memory T cells, we studied skin biopsies and HSV-2-reactive CD4+ T cells from PBMCs by T cell receptor (TCR) β chain (TRB) sequencing before and after vaccination with a replication-incompetent whole-virus HSV-2 vaccine candidate (HSV529). The representation of HSV-2-reactive CD4+ TRB sequences from PBMCs in the skin TRB repertoire increased after the first vaccine dose. We found sustained expansion after vaccination of unique, skin-based T cell clonotypes that were not detected in HSV-2-reactive CD4+ T cells isolated from PBMCs. In one participant, a switch in immunodominance occurred with the emergence of a TCR αβ pair after vaccination that was not detected in blood. This TCRαβ was shown to be HSV-2 reactive by expression of a synthetic TCR in a Jurkat-based NR4A1 reporter system. The skin in areas of HSV-2 reactivation possessed an oligoclonal TRB repertoire that was distinct from the circulation. Defining the influence of therapeutic vaccination on the HSV-2-specific TRB repertoire requires tissue-based evaluation.
在单纯疱疹病毒 2 （HSV-2）再激活部位的皮肤富含 HSV-2 特异性 T 细胞。为了评估免疫治疗性疫苗是否能引发基于皮肤的记忆 T 细胞，我们通过 T 细胞受体（TCR）β链（TRB）测序，在接种复制缺陷型全病毒 HSV-2 候选疫苗（HSV529）前后，研究了皮肤活检和外周血单个核细胞（PBMC）中的 HSV-2 反应性 CD4+ T 细胞。接种第一剂疫苗后，皮肤 TRB 库中源自 PBMC 的 HSV-2 反应性 CD4+ TRB 序列的代表性增加。我们发现，在接种疫苗后，独特的、基于皮肤的 T 细胞克隆型持续扩增，而这些克隆型在 PBMC 中分离的 HSV-2 反应性 CD4+ T 细胞中并未检测到。在一名参与者中，接种疫苗后出现了免疫优势的转变，出现了一种在血液中未检测到的 TCRαβ对。通过在基于 Jurkat 的 NR4A1 报告系统中表达合成 TCR，证明了该 TCRαβ 对 HSV-2 具有反应性。在 HSV-2 再激活部位的皮肤中存在一种与循环不同的寡克隆 TRB 库。定义治疗性疫苗对 HSV-2 特异性 TRB 库的影响需要基于组织的评估。
