Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues

Mol Ther. 2014 Mar;22(3):675-684. doi: 10.1038/mt.2013.274. Epub 2013 Dec 5.


A substudy of a phase I/II, prospective, multicenter clinical trial was carried out to investigate the potential benefit of therapeutic vaccination on hepatitis B e antigen-negative patients with chronic hepatitis B (CHB), treated efficiently with analogues. Patients were randomized in 2 arms, one receiving a hepatitis B virus (HBV) envelope DNA vaccine, and one without vaccination. At baseline, HBV-specific interferon (IFN)-γ-producing T cells were detected in both groups after in vitro expansion of peripheral blood mononuclear cells. Vaccine-specific responses remained stable in the vaccine group, whereas in the control group the percentage of patients with HBV-specific IFN-γ-producing T cells decreased over time. The vaccine-specific cytokine-producing T cells were mostly polyfunctional CD4(+) T cells, and the proportion of triple cytokine-producer T cells was boosted after DNA injections. However, these T-cell responses did not impact on HBV reactivation after stopping analogue treatment. Importantly, before cessation of treatment serum hepatitis B surface antigen (HBsAg) titers were significantly associated with DNA or HBsAg clearance. Therapeutic vaccination in CHB patients with persistent suppression of HBV replication led to the persistence of T-cell responses, but further improvements should be searched for to control infection after treatment discontinuation.

Trial registration: NCT00536627.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Combined Modality Therapy
  • DNA, Viral / genetics
  • Female
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / immunology
  • Hepatitis B Vaccines / therapeutic use
  • Hepatitis B e Antigens / therapeutic use*
  • Hepatitis B virus / growth & development*
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / therapy*
  • Humans
  • Interferon-gamma / metabolism*
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocytes / immunology*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use*
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / metabolism
  • Viral Load / immunology


  • DNA, Viral
  • Hepatitis B Vaccines
  • Hepatitis B e Antigens
  • Vaccines, DNA
  • Viral Envelope Proteins
  • Interferon-gamma

Associated data