title: A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy.
abstract: A DNA vaccine against the hepatitis B virus (HBV), enhanced by IL-2/IFN-γ fusion protein expression from a plasmid construct and mediated by in vivo electroporation, was evaluated in a total of 39 HBeAg-positive patients with chronic hepatitis B (CHB). The six of 39 patients with a serum alanine aminotransferase (ALT) value of 1-2 times upper limit of normal (ULN) were assigned to the open-label arm (Group01) receiving vaccine monotherapy; the remaining 33 patients with an ALT of more than two times ULN were enroled to the randomized and controlled arm (Group02) receiving lamivudine (LAM) monotherapy (LAM+placebo) or combined therapy (LAM+DNA vaccine) in 1:2 ratio. In Group01, a significant elevation of HBV-specific IFN-γ-secreting T-cell counts in comparison with baseline was observed. In Group02, the proportion of patients with HBV DNA suppression was higher with LAM+DNA vaccine than with LAM monotherapy at each visit time point after the final injection of DNA vaccine at week 36, revealing a significant difference between the two groups (P = 0.03) at week 60. The incidence of dual-site mutations of rtM204/I/S+rtL180M was significantly lower (P = 0.03) with an identified lower virological breakthrough (VBT) rate (P = 0.03) in patients receiving LAM+DNA vaccine than LAM monotherapy, accompanied with a significant higher positive T-cell response rate in patients receiving LAM+DNA vaccine (P = 0.03). In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective, and that the HBV-specific T-cell responses induced by DNA vaccination under LAM chemotherapy showed a correlation with the suppression of viral replication in patients with CHB.
authors: Liver Disease Research Center, Guangzhou 458 Hospital, Guangzhou, China.
authors: F-Q
authors: FQ
authors: Yang
authors: Y-Y
authors: YY
authors: Yu
authors: G-Q
authors: GQ
authors: Wang
authors: J
authors: J
authors: Chen
authors: J-H
authors: JH
authors: Li
authors: Y-Q
authors: YQ
authors: Li
authors: G-R
authors: GR
authors: Rao
authors: G-Y
authors: GY
authors: Mo
authors: X-R
authors: XR
authors: Luo
authors: G-M
authors: GM
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004358:Drug Therapy / Q000379:methods; D018274:Electroporation; D005260:Female; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D017325:Hepatitis B Vaccines; D010919:Placebos; D019444:Vaccines, DNA; D019259:Lamivudine; D007371:Interferon-gamma; D000410:Alanine Transaminase