title: Correlation of antiviral T-cell responses with suppression of viral rebound in chronic hepatitis B carriers: a proof-of-concept study.
abstract: Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-gamma secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4(+) memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.
authors.affiliation: Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Yang
authors.forename: C-G
authors.initials: CG
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.forename: S-J
authors.initials: SJ
authors.lastname: Im
authors.forename: Y-M
authors.initials: YM
authors.lastname: Kim
authors.forename: J-M
authors.initials: JM
authors.lastname: Son
authors.forename: J-S
authors.initials: JS
authors.lastname: Wang
authors.forename: S-K
authors.initials: SK
authors.lastname: Yoon
authors.forename: M-K
authors.initials: MK
authors.lastname: Song
authors.forename: A
authors.initials: A
authors.lastname: Ambrozaitis
authors.forename: N
authors.initials: N
authors.lastname: Kharchenko
authors.forename: Y-D
authors.initials: YD
authors.lastname: Yun
authors.forename: C-M
authors.initials: CM
authors.lastname: Kim
authors.forename: C-Y
authors.initials: CY
authors.lastname: Kim
authors.forename: S-H
authors.initials: SH
authors.lastname: Lee
authors.forename: B-M
authors.initials: BM
authors.lastname: Kim
authors.forename: W-B
authors.initials: WB
authors.lastname: Kim
authors.forename: Y-C
authors.initials: YC
authors.lastname: Sung
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D006579:Heterozygote; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12; D019259:Lamivudine; D007371:Interferon-gamma