title: Safety and immunogenicity of therapeutic DNA vaccine with antiviral drug in chronic HBV patients and its immunogenicity in mice.
abstract: OBJECTIVE
  Here, we evaluated the safety and immunogenicity of hepatitis B virus (HBV) DNA vaccine, HB-110, in mice and Korean patients with chronic hepatitis B (CHB) undergoing adefovir dipivoxil (ADV) treatment.
  
  
  METHODS
  For animal study, mice (BALB/c or HBV transgenic) were immunized with mHB-110, and T-cell and antibody responses were evaluated. For clinical study, 27 patients randomly received either ADV alone or ADV in combination with HB-110. Liver function tests, serum HBV DNA levels and the presence of HBeAg/anti-HBe were analysed. T-cell responses were estimated by ELISPOT and FACS analysis.
  
  
  RESULTS
  mHB-110 induced higher T-cell and antibody responses than mHB-100 in mice. No adverse effects were observed by HB-110 cotreated with ADV. HBV-specific T-cell responses were induced in a portion of patients in medium to high dose of HB-110. Interestingly, HB-110 exhibited positive effects on ALT normalization and maintenance of HBeAg seroconversion. One patient, who received high dose of HB-110 exhibited HBeAg seroconversion during vaccination, which correlated with vaccine-induced T-cell responses without ALT elevation.
  
  
  CONCLUSIONS
  HB-110 was safe and tolerable in CHB patients. In contrast to results in animal models, HB-110 in Korean patients exhibited weaker capability of inducing HBV-specific T-cell responses and HBeAg seroconversion than HB-100 in Caucasian patients. As Asian patients, who are generally infected via vertical transmission, appeared to have higher level of immune tolerance than Caucasian, novel approaches for breaking immune tolerance rather than enhancing immunogenicity may be more urgently demanded to develop effective therapeutic HBV DNA vaccines.
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Seo
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Im
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.forename: Myeong Jun
authors.initials: MJ
authors.lastname: Song
authors.forename: Chan Ran
authors.initials: CR
authors.lastname: You
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Jang
authors.forename: Se Hwan
authors.initials: SH
authors.lastname: Yang
authors.forename: You Suk
authors.initials: YS
authors.lastname: Suh
authors.forename: Ji Soo
authors.initials: JS
authors.lastname: Song
authors.forename: Byong Moon
authors.initials: BM
authors.lastname: Kim
authors.forename: Chae Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Sook Hyang
authors.initials: SH
authors.lastname: Jeong
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000818:Animals; D000917:Antibody Formation; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019444:Vaccines, DNA; D000225:Adenine; C106812:adefovir dipivoxil
keywords: DNA vaccine; T-cell response; chronic infection; hepatitis B; phase I