{"doi":"10.3389/fimmu.2021.645299","title":"Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed","abstract":"Advances in high-throughput sequencing have revolutionized the manner with which we can study T cell responses. We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion. By performing bulk T cell receptor (TCR) β deep sequencing of peripheral blood mononuclear cells before and after 4 vaccinations, 70 putatively vaccine-specific clonotypes were identified for being significantly increased using a beta-binomial model. In order to verify the vaccine-specificity of these clonotypes, T cells with specificity to a region, HPV 16 E6 91-115, previously identified to be vaccine-induced using an interferon-γ enzyme-linked immunospot assay, were sorted and analyzed using single-cell RNA-seq and TCR sequencing. HPV specificity in 60 of the 70 clonotypes identified to be vaccine-specific was demonstrated. TCR β bulk sequencing of the cervical liquid-based cytology samples and cervical formalin-fixed paraffin-embedded samples before and after 4 vaccinations demonstrated the presence of these HPV-specific T cells in the cervix. Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells not only in the periphery but also in the cervix. Such an approach should be useful as a novel approach to assess vaccine-specific responses in various anatomical areas.","journal":"Frontiers in Immunology","year":2021,"id":190340,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":333780,"name":"Sumit K. Shah","orcid":"0000-0003-2916-8045","position":1,"is_corresponding":false},{"id":586287,"name":"Teresa Evans","orcid":null,"position":2,"is_corresponding":false},{"id":564226,"name":"Hannah Coleman","orcid":null,"position":3,"is_corresponding":false},{"id":333782,"name":"Benjamin J. Lieblong","orcid":"0000-0001-7225-7049","position":4,"is_corresponding":false},{"id":585527,"name":"Horace J. Spencer","orcid":"0000-0001-8176-881X","position":5,"is_corresponding":false},{"id":586288,"name":"Charles M. Quick","orcid":null,"position":6,"is_corresponding":false},{"id":563806,"name":"Toshiyuki Sasagawa","orcid":"0000-0002-8480-844X","position":7,"is_corresponding":false},{"id":484900,"name":"Owen Stephens","orcid":"0000-0001-8400-2916","position":8,"is_corresponding":false},{"id":572512,"name":"Erich A. Peterson","orcid":"0000-0003-0925-7243","position":9,"is_corresponding":false},{"id":283869,"name":"Donald J. Johann","orcid":null,"position":10,"is_corresponding":false},{"id":585528,"name":"Yong‐Chen Lu","orcid":"0000-0002-0275-9825","position":11,"is_corresponding":false},{"id":333781,"name":"Mayumi Nakagawa","orcid":"0000-0002-0377-4613","position":12,"is_corresponding":false},{"id":563804,"name":"Takeo Shibata","orcid":"0000-0002-5569-9301","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:49:26.966524Z","pmid":"34659195","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":[]}