{"doi":"10.1101/2022.02.04.22270210","title":"Expansion of the HSV-2-specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine","abstract":"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 peripheral blood mononuclear cells (PBMCs) by T cell receptor β ( 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 T cell receptor (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 possesses an oligoclonal TRB repertoire that is distinct from the circulation. Defining the influence of therapeutic vaccination on the HSV-2-specific TRB repertoire requires tissue-based evaluation.","journal":"medRxiv","year":2022,"id":300878,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":673086,"name":"Alvason Li","orcid":null,"position":1,"is_corresponding":false},{"id":430028,"name":"Kerry J. Laing","orcid":"0000-0001-9245-5325","position":2,"is_corresponding":false},{"id":431161,"name":"Lichun Dong","orcid":null,"position":3,"is_corresponding":false},{"id":673085,"name":"Kurt Diem","orcid":null,"position":4,"is_corresponding":false},{"id":294665,"name":"Lichen Jing","orcid":"0000-0002-5938-4171","position":5,"is_corresponding":false},{"id":879358,"name":"Krithi Basu","orcid":null,"position":6,"is_corresponding":false},{"id":472356,"name":"Mariliis Ott","orcid":null,"position":7,"is_corresponding":false},{"id":709711,"name":"Jim Tartaglia","orcid":null,"position":8,"is_corresponding":false},{"id":991804,"name":"Sanjay Gurunathan","orcid":"0009-0007-7241-6370","position":9,"is_corresponding":false},{"id":991805,"name":"Jack L. Reid","orcid":"0009-0005-8080-8302","position":10,"is_corresponding":false},{"id":474686,"name":"Matyas Ecsedi","orcid":"0000-0003-1341-8070","position":11,"is_corresponding":false},{"id":471437,"name":"Aude G. Chapuis","orcid":"0000-0002-9574-5448","position":12,"is_corresponding":false},{"id":301546,"name":"Meei‐Li Huang","orcid":"0000-0003-2058-2776","position":13,"is_corresponding":false},{"id":486167,"name":"Amalia Magaret","orcid":"0000-0002-1221-3746","position":14,"is_corresponding":false},{"id":473787,"name":"Christine Johnston","orcid":"0000-0002-3073-0843","position":15,"is_corresponding":false},{"id":672220,"name":"Jia Zhu","orcid":"0000-0002-8676-5105","position":16,"is_corresponding":false},{"id":294672,"name":"David M. Koelle","orcid":"0000-0003-1255-9023","position":17,"is_corresponding":false},{"id":96348,"name":"Lawrence Corey","orcid":"0000-0002-2179-2436","position":18,"is_corresponding":false},{"id":582717,"name":"Emily S. Ford","orcid":"0000-0001-7358-798X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:31:57.812980Z","pmid":"38352384","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}