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Expansion of the HSV-2-specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine.
- Source :
-
JCI insight [JCI Insight] 2024 Jun 18; Vol. 9 (14). Date of Electronic Publication: 2024 Jun 18. - Publication Year :
- 2024
-
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.
- Subjects :
- Humans
Female
Receptors, Antigen, T-Cell, alpha-beta immunology
Receptors, Antigen, T-Cell, alpha-beta genetics
Male
Adult
Vaccination
Middle Aged
Herpesvirus 2, Human immunology
Skin immunology
Skin virology
Herpes Genitalis immunology
Herpes Genitalis prevention & control
Herpes Genitalis virology
CD4-Positive T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 9
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 39133650
- Full Text :
- https://doi.org/10.1172/jci.insight.179010