{"doi":"10.1016/j.jhep.2020.02.009","title":"IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses","abstract":null,"journal":"Journal of Hepatology","year":2020,"id":609509,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1566674,"name":"Pil Soo Sung","orcid":null,"position":1,"is_corresponding":false},{"id":451532,"name":"Seon-Hui Hong","orcid":"0000-0002-0746-9237","position":2,"is_corresponding":false},{"id":1565761,"name":"Hoyoung Lee","orcid":"0000-0003-1266-7147","position":3,"is_corresponding":false},{"id":1566675,"name":"June Young Koh","orcid":null,"position":4,"is_corresponding":false},{"id":1512783,"name":"Hyojin Lee","orcid":"0000-0002-5560-0041","position":5,"is_corresponding":false},{"id":1566676,"name":"Scott White","orcid":null,"position":6,"is_corresponding":false},{"id":1566677,"name":"Joel N. Maslow","orcid":null,"position":7,"is_corresponding":false},{"id":331754,"name":"David B. Weiner","orcid":"0000-0002-2232-8512","position":8,"is_corresponding":false},{"id":1039063,"name":"Su‐Hyung Park","orcid":"0000-0001-6363-7736","position":9,"is_corresponding":false},{"id":1566678,"name":"Moonsup Jeong","orcid":"0000-0001-8332-4606","position":10,"is_corresponding":false},{"id":845145,"name":"Jeong Heo","orcid":"0000-0003-0961-7851","position":11,"is_corresponding":false},{"id":776396,"name":"Sang Hoon Ahn","orcid":"0000-0002-3629-4624","position":12,"is_corresponding":false},{"id":666400,"name":"Eui‐Cheol Shin","orcid":"0000-0002-6308-9503","position":13,"is_corresponding":false},{"id":120260,"name":"Ji Won Han","orcid":"0000-0003-1456-1450","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses","abstract":"<h4>Background & aims</h4>Although direct-acting antiviral (DAA) treatment results in a sustained virologic response (SVR) in most patients with chronic HCV infection, they are at risk of re-infection. Moreover, the immune system is not completely normalized even after SVR (e.g. increased regulatory T [Treg] cell frequency). We developed a DNA vaccine, GLS-6150, to prevent re-infection of patients with DAA-induced SVR and evaluated its safety and immunogenicity in individuals with chronic HCV infection.<h4>Methods</h4>GLS-6150 consists of plasmids encoding HCV non-structural proteins (NS3-NS5A) and adjuvant IFNL3. The vaccine was administered 4 times at 4-weekly intervals to 3 groups (1, 3, or 6 mg/vaccination; n = 6 per group), followed by a 6 mg boost at 24 weeks (n = 14). Peripheral blood T cell responses were evaluated by interferon (IFN)-γ enzyme-linked immunospot assays, intracellular cytokine staining, and major histocompatibility complex class-I (MHC-I) dextramer staining. Treg cell frequency was assessed by flow cytometry.<h4>Results</h4>Severe adverse events or vaccine discontinuation were not reported. The IFN-γ spot-forming cells specific to NS3-NS5A were increased by GLS-6150. Both CD4<sup>+</sup> and CD8<sup>+</sup> T cells produced multiple cytokines. However, the frequency and phenotype of HCV-specific MHC-I dextramer<sup>+</sup>CD8<sup>+</sup> T cells were not changed. Interestingly, the frequency of Treg cells, particularly activated Treg cells, was decreased by GLS-6150, as expected from previous reports that IFNL3 adjuvants decrease Treg cell frequency. Ex vivo IFN-λ3 treatment reduced Treg frequency in pre-vaccination peripheral blood mononuclear cells. Finally, Treg cell frequency inversely correlated with HCV-specific, IFN-γ-producing T cell responses in the study participants.<h4>Conclusions</h4>We demonstrate that GLS-6150 decreases Treg cell frequency and enhances HCV-specific T cell responses without significant side effects. A phase I clinical trial of GLS-6150 is currently underway in patients with DAA-induced SVR.<h4>Clinical trial number</h4>NCT02027116.<h4>Lay summary</h4>Although direct-acting antivirals (DAAs) are successfully used for the treatment of chronic hepatitis C virus (HCV) infection, a prophylactic HCV vaccine needs to be developed, especially for patients who achieve a sustained virologic response. In the current study, we show that a DNA vaccine (GLS-6150) was safe and increased HCV-specific T cell responses. A clinical trial is underway to test this vaccine in patients with a sustained virologic response following DAA therapy.","is_dataset_classified":null,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32088322","pmcid":null,"openalex_id":"https://openalex.org/W3006934915","authors":[],"funders":[{"funder_name":"GeneOne Life Science, Inc","grant_id":"","title":null}],"total_grants":1,"fwci":1.5938,"citation_percentile":0.83847701,"influential_citations":0,"citation_trend":[{"year":2020,"count":2},{"year":2021,"count":7},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":5},{"year":2025,"count":5},{"year":2026,"count":5}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0168827820301070?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0168827820301070?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.jhep.2020.02.009","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32088322","host_type":"repository"}],"fields_of_study":["Hepatitis C virus research","interferon and immune responses","HIV Research and Treatment","Adjuvants, Immunologic","Antiviral Agents","CD4-Positive T-Lymphocytes","CD8-Positive T-Lymphocytes","Drug Monitoring","Female","Hepacivirus","Hepatitis C, Chronic","Humans","Interferons","Male","Middle Aged","Monitoring, Immunologic","Secondary Prevention","Sustained Virologic Response","T-Lymphocytes, Regulatory","Vaccines, DNA","Virus Activation","Interleukins","Interferon Lambda"],"mesh_terms":["Sustained Virologic Response","Interferon Lambda","Adjuvants, Immunologic","Antiviral Agents","Female","Humans","Interferons","Interleukins","Male","Middle Aged","Virus Activation","Monitoring, Immunologic","CD4-Positive T-Lymphocytes","Hepacivirus","Drug Monitoring","CD8-Positive T-Lymphocytes","Vaccines, DNA","Hepatitis C, Chronic","T-Lymphocytes, Regulatory","Secondary Prevention"],"keywords":["Immunology","CD8","Immune system","Immunogenicity","Medicine","T cell","Regulatory T cell","Adjuvant","FOXP3","Peripheral blood mononuclear cell","DNA vaccination","Virology","Biology","IL-2 receptor","Immunization","T cells","DNA vaccine","Chronic hepatitis C","Ifnl3"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T09:00:04.118331Z","pmid":null,"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":[]}