{"doi":"10.3389/fimmu.2020.00479","title":"Rapid Induction and Maintenance of Virus-Specific CD8+ TEMRA and CD4+ TEM Cells Following Protective Vaccination Against Dengue Virus Challenge in Humans","abstract":"Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious human disease. The current lack of an effective vaccine to simultaneously protect against the four serotypes of DENV in seronegative individuals is a major unmet medical need. Further, the immunological basis for protective immunity in the setting of DENV infection or vaccination is not fully understood. Our team has developed a live attenuated tetravalent dengue virus vaccine that provides complete protection in a human model of dengue virus challenge. The goal of this study was to define, in the context of protective human vaccination, the quality of vaccine-induced DENV-specific CD8+ and CD4+ T cells and the temporal dynamics associated with their formation and maintenance. Multifunctional, DENV-specific CD8+ and CD4+ T cells developed eight to 14 days after vaccination and were maintained for at least six months. Virus-specific CD8 T+ cells were a mixture of effector memory T cells (TEM) and effector memory T cells re-expressing CD45RA (TEMRA), with TEM cells predominating until day 21 post-vaccination and TEMRA cells thereafter. The majority of virus-specific CD4+ T cells were TEM with a small fraction being TEMRA. The frequency of virus-specific CD8+ and CD4+ T cells were further skewed to the TEMRA phenotype following either a second dose of the tetravalent vaccine or challenge with a single serotype of DENV. Collectively, our study has defined the phenotypic profile of antiviral CD8+ and CD4+ T cells associated with protective immunity to DENV infection and the kinetics of their formation and maintenance.","journal":"Frontiers in Immunology","year":2020,"id":67287,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":357574,"name":"Phil Eisenhauer","orcid":null,"position":1,"is_corresponding":false},{"id":246856,"name":"Sean A. Diehl","orcid":"0000-0001-9700-235X","position":2,"is_corresponding":false},{"id":338272,"name":"Kristen K. Pierce","orcid":null,"position":3,"is_corresponding":false},{"id":342842,"name":"Stephen S. Whitehead","orcid":"0000-0001-6707-482X","position":4,"is_corresponding":false},{"id":342841,"name":"Anna P. Durbin","orcid":"0000-0002-6652-2851","position":5,"is_corresponding":false},{"id":246860,"name":"Beth D. Kirkpatrick","orcid":"0000-0002-7016-7338","position":6,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":7,"is_corresponding":false},{"id":103766,"name":"Daniela Weiskopf","orcid":"0000-0003-2968-7371","position":8,"is_corresponding":false},{"id":356384,"name":"Jonathan E. Boyson","orcid":"0000-0003-2673-9148","position":9,"is_corresponding":false},{"id":109810,"name":"Jason Botten","orcid":"0000-0001-6839-0306","position":10,"is_corresponding":false},{"id":357573,"name":"Nancy Graham","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T21:15:12.020735Z","pmid":"32265929","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":[]}