%0 Journal Article
%T Expansion of the HSV-2-specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine.
%A Ford ES
%A Li AZ
%A Laing KJ
%A Dong L
%A Diem K
%A Jing L
%A Mayer-Blackwell K
%A Basu K
%A Ott M
%A Tartaglia J
%A Gurunathan S
%A Reid JL
%A Ecsedi M
%A Chapuis AG
%A Huang ML
%A Magaret AS
%A Johnston C
%A Zhu J
%A Koelle DM
%A Corey L
%J JCI Insight
%V 9
%N 14
%D 2024 Jun 18
%M 39133650
%F 9.484
%R 10.1172/jci.insight.179010
%X 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.