title: Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis B.
abstract: OBJECTIVE
  The safety and clinical efficacy of a vaccine containing both hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (HBsAg/HBcAg) were evaluated in patients with chronic hepatitis B (CHB).
  
  
  METHODS
  Eighteen patients with CHB were administered a vaccine containing 100 μg of HBsAg and 100 μg of HBcAg. The vaccine was administered ten times at 2-weekly intervals, the first five times via the nasal route only and the subsequent five times via both nasal and subcutaneous routes. The safety and efficacy of this therapeutic approach were assessed by periodic assessment of the patients' general condition, viral kinetics, and biochemical parameters during treatment and 24 and 48 weeks after therapy. The production of cytokines by peripheral blood mononuclear cells (PBMC) and antigen-pulsed dendritic cells (DC) was evaluated to assess the immunomodulatory effects of the HBsAg/HBcAg vaccine in CHB patients.
  
  
  RESULTS
  The HBsAg/HBcAg vaccine was safe in all patients. No flare of HBV DNA or alanine aminotransferase (ALT) was recorded in any patient. Sustained HBV DNA negativity and persistently normalized ALT were detected in 9 (50 %) and 18 (100 %) patients with CHB, respectively. PBMC and HBsAg/HBcAg-pulsed DCs from HBsAg/HBcAg-vaccinated CHB patients produced significantly higher levels of various cytokines [interleukin 1β (IL-1β), IL-6, IL-8, IL-12, and tumor necrosis factor α (TNF-α)] than those from control unvaccinated CHB patients (p < 0.05) after stimulation with HBsAg/HBcAg in vitro.
  
  
  CONCLUSIONS
  HBsAg/HBcAg vaccine seems a safe and efficient therapeutic approach for patients with CHB.
authors.affiliation: Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. shwapnil@agni.com.
authors.forename: Mamun
authors.initials: M
authors.lastname: Al-Mahtab
authors.affiliation: Department of Medical Sciences, Toshiba General Hospital, Higashi Oi 6-3-22, Tokyo, 140-8522, Japan. sheikh.akbar@po.toshiba.co.jp.
authors.forename: Sheikh Mohammad Fazle
authors.initials: SM
authors.lastname: Akbar
authors.affiliation: Center for Genetic Engineering and Biotechnology, Havana, Cuba. julio.aguilar@cigb.edu.cu.
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Aguilar
authors.affiliation: Clinical Research Organization, Dhaka, Bangladesh. uddinhelal1970@gmail.com.
authors.forename: Md Helal
authors.initials: MH
authors.lastname: Uddin
authors.affiliation: Bangladesh Agricultural University, Mymensign, Bangladesh. sakirul.khan@gmail.com.
authors.forename: Md Sakirul Islam
authors.initials: MS
authors.lastname: Khan
authors.affiliation: Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. salimur51@yahoo.com.
authors.forename: Salimur
authors.initials: S
authors.lastname: Rahman
keywords: Chronic hepatitis B; HBsAg/HBcAg vaccine; Immunotherapy; Therapeutic vaccine