title: Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues.
abstract: 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.
authors.affiliation: Départment de Virologie, Institut Pasteur, Laboratoire de pathogénèse des virus de l'hépatite B and INSERM U845, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Godon
authors.affiliation: Institut Cochin, CNRS (UMR 8104) and INSERM U-1016, Université Paris Descartes, et Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, Cochin Hospital, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Kahi
authors.affiliation: Virology Unit, Cochin Hospital, Paris, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Meritet
authors.affiliation: Départment de Virologie, Institut Pasteur, Unité des Régulations des Infections rétrovirales, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Scott-Algara
authors.affiliation: Institut Cochin, CNRS (UMR 8104) and INSERM U-1016, Université Paris Descartes, et Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, Cochin Hospital, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Pol
authors.affiliation: Départment de Virologie, Institut Pasteur, Laboratoire de pathogénèse des virus de l'hépatite B and INSERM U845, Paris, France.
authors.forename: M L
authors.initials: ML
authors.lastname: Michel
authors.affiliation: Départment de Virologie, Institut Pasteur, Laboratoire de pathogénèse des virus de l'hépatite B and INSERM U845, Paris, France. Electronic address: maryline.bourgine@pasteur.fr.
authors.forename: M
authors.initials: M
authors.lastname: Bourgine
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000254:growth & development*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D019562:Viral Load / Q000276:immunology
chemical_list: D004279:DNA, Viral; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D007371:Interferon-gamma