title: Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers.
abstract: 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.
authors.affiliation: 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
authors.forename: Maryline
authors.initials: M
authors.lastname: Mancini-Bourgine
authors.forename: Héléne
authors.initials: H
authors.lastname: Fontaine
authors.forename: Christian
authors.initials: C
authors.lastname: Bréchot
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Michel
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis; D002353:Carrier State; D004797:Enzyme-Linked Immunosorbent Assay; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma