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A pilot randomized controlled trial of dual‐plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy
Author(s) -
Yang F.Q.,
Yu Y.Y.,
Wang G.Q.,
Chen J.,
Li J.H.,
Li Y.Q.,
Rao G.R.,
Mo G.Y.,
Luo X.R.,
Chen G.M.
Publication year - 2012
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2012.01589.x
Subject(s) - lamivudine , medicine , dna vaccination , hbeag , virology , hepatitis b virus , hepatitis b , hbsag , vaccination , gastroenterology , immunology , antibody , virus , immunization
Summary. 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.