Cited 17 times in
IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses
DC Field | Value | Language |
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dc.contributor.author | 안상훈 | - |
dc.date.accessioned | 2020-12-01T17:28:36Z | - |
dc.date.available | 2020-12-01T17:28:36Z | - |
dc.date.issued | 2020-07 | - |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/180287 | - |
dc.description.abstract | Background & aims: 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. Methods: 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. Results: 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+ and CD8+ T cells produced multiple cytokines. However, the frequency and phenotype of HCV-specific MHC-I dextramer+CD8+ 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. Conclusions: 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. Clinical trial number: NCT02027116. Lay summary: 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. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Elsevier | - |
dc.relation.isPartOf | JOURNAL OF HEPATOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Ji Won Han | - |
dc.contributor.googleauthor | Pil Soo Sung | - |
dc.contributor.googleauthor | Seon-Hui Hong | - |
dc.contributor.googleauthor | Hoyoung Lee | - |
dc.contributor.googleauthor | June Young Koh | - |
dc.contributor.googleauthor | Hyojin Lee | - |
dc.contributor.googleauthor | Scott White | - |
dc.contributor.googleauthor | Joel N Maslow | - |
dc.contributor.googleauthor | David B Weiner | - |
dc.contributor.googleauthor | Su-Hyung Park | - |
dc.contributor.googleauthor | Moonsup Jeong | - |
dc.contributor.googleauthor | Jeong Heo | - |
dc.contributor.googleauthor | Sang Hoon Ahn | - |
dc.contributor.googleauthor | Eui-Cheol Shin | - |
dc.identifier.doi | 10.1016/j.jhep.2020.02.009 | - |
dc.contributor.localId | A02226 | - |
dc.relation.journalcode | J01441 | - |
dc.identifier.eissn | 1600-0641 | - |
dc.identifier.pmid | 32088322 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0168827820301070 | - |
dc.subject.keyword | Chronic hepatitis C | - |
dc.subject.keyword | DNA vaccine | - |
dc.subject.keyword | IFNL3 | - |
dc.subject.keyword | Regulatory T cell | - |
dc.subject.keyword | T cells | - |
dc.contributor.alternativeName | Ahn, Sang Hoon | - |
dc.contributor.affiliatedAuthor | 안상훈 | - |
dc.citation.volume | 73 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 72 | - |
dc.citation.endPage | 83 | - |
dc.identifier.bibliographicCitation | JOURNAL OF HEPATOLOGY, Vol.73(1) : 72-83, 2020-07 | - |
dc.identifier.rimsid | 67115 | - |
dc.type.rims | ART | - |
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