{Reference Type}: Journal Article
{Title}: Expansion of the HSV-2-specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine.
{Author}: Ford ES;Li AZ;Laing KJ;Dong L;Diem K;Jing L;Mayer-Blackwell K;Basu K;Ott M;Tartaglia J;Gurunathan S;Reid JL;Ecsedi M;Chapuis AG;Huang ML;Magaret AS;Johnston C;Zhu J;Koelle DM;Corey L;
{Journal}: JCI Insight
{Volume}: 9
{Issue}: 14
{Year}: 2024 Jun 18
{Factor}: 9.484
{DOI}: 10.1172/jci.insight.179010
{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.