Expansion of the HSV-2–specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine

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Abstract

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.

Authors

Emily S. Ford, Alvason Z. Li, Kerry J. Laing, Lichun Dong, Kurt Diem, Lichen Jing, Koshlan Mayer-Blackwell, Krithi Basu, Mariliis Ott, Jim Tartaglia, Sanjay Gurunathan, Jack L. Reid, Matyas Ecsedi, Aude G. Chapuis, Meei-Li Huang, Amalia S. Magaret, Christine Johnston, Jia Zhu, David M. Koelle, Lawrence Corey