Hepatitis Research Today is a free monthly online journal that collates and summarizes the latest research about Hepatitis, including details on hepatitis a, b, c, causes, symptoms.

Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers.

Mancini-Bourgine M, Fontaine H, Bréchot C, Pol S, Michel ML

Carcinogénèse Hépatique et Virologie Moléculaire, Institut National de la Santé et de la Recherche Médicale Unité 370, Département de Médecine Moléculaire, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris, France. mmancini@pasteur.fr

Hepatitis B virus (HBV) is the major pathogen of chronic hepatitis and liver disease worldwide. Despite the availability of effective vaccines against hepatitis B for many years, over 370 million people remain persistently infected with HBV. Viral persistence is thought to be related to poor HBV-specific T-cell responses. Based on clinical data, the development of efficient methods capable of inducing strong T-cell responses is an important and primary step toward the development of immunotherapeutics against chronic HBV infection. We designed a phase I clinical trial in chronic HBV carriers to assess safety, tolerability and immunogenicity of a DNA vaccine expressing HBV small (S) and middle (preS2 +S) envelope proteins. After occurrence of lamivudine breakthrough, 10 HBeAg positive patients with chronic hepatitis B were followed longitudinally before, during and after DNA vaccine therapy. Immunizations were well tolerated and adverse physical events were mild and considered unrelated to the vaccine. Proliferative responses to hepatitis B surface antigen (HBsAg) were detected in two patients after DNA injections. Following three injections of vaccine, interferon (IFN)-gamma-producing T-cells specific for the preS2 or the S antigen were detectable in 50 and 100% of the patients, respectively. Each patient recognized at least one peptide within the envelope domain encoded by the vaccine. Anti-preS2 antibodies and seroconversion to anti-HBe were detected in two patients. This study shows evidences for the safety and immunological efficacy of HBV-DNA vaccination and demonstrates that DNA vaccination can restore or activate T-cell responses in chronic HBV carriers.

Published 1 June 2006 in Vaccine, 24(21): 4482-9.
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