A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy
- F.-Q. Yang1,†,
- Y.-Y. Yu2,†,
- G.-Q. Wang2,
- J. Chen3,
- J.-H. Li4,
- Y.-Q. Li5,
- G.-R. Rao1,
- G.-Y. Mo1,
- X.-R. Luo1,
- G.-M. Chen1
Article first published online: 26 FEB 2012 - 1 Liver Disease Research Center, Guangzhou 458 Hospital, Guangzhou, China
- 2 Department of Infectious Diseases, Peking University First Hospital, Beijing, China
- 3 Ditan Hospital, Beijing, China
- 4 Youan Hospital, Beijing, China
- 5 Beijing 302 Hospital, Beijing, China
- † These authors contributed equally to this paper.
*Xian-Rong Luo and Guang-Ming Chen, Liver Disease Research Center, Guangzhou 458 Hospital, Guangzhou 510600, China. E-mail: [email protected] Keywords:- chronic hepatitis B;
- DNA vaccine;
- hepatitis B virus;
- lamivudine-resistant mutants;
- T cell
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.
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发表于 2012-7-26 06:32
