title: Immunological monitoring during therapeutic vaccination as a prerequisite for the design of new effective therapies: induction of a vaccine-specific CD4+ T-cell proliferative response in chronic hepatitis B carriers.
abstract: We characterized the anti-viral T-cell response in 22 chronically infected patients, who participated in a European multi-center randomized placebo-controlled, double-blind study therapeutic vaccination trial with pre-S1, pre-S2 and S antigenic components of the hepatitis B virus (HBV). It induced a significant HBsAg-specific T-cell proliferation and the production of Th2-cytokines (i.e. IL-5). A specific induction of Th1-lymphokines was not detectable although this has been demonstrated in this study in response to the nucleocapsid protein (HBcAg). Further analysis indicated that this approach does not activate HBV-specific CD8+ T-lymphocytes as detected by ELISPOT-assay. Our results might explain why a specific therapeutic vaccine, although safe and well-tolerated is not always able to break tolerance leading to the clearance of the hepatitis B virus.
authors.affiliation: Medical Department II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. maria-christina.jung@med2.med.uni-muenchen.de
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Jung
authors.forename: Norbert
authors.initials: N
authors.lastname: Grüner
authors.forename: Reinhart
authors.initials: R
authors.lastname: Zachoval
authors.forename: Winfried
authors.initials: W
authors.lastname: Schraut
authors.forename: Tilman
authors.initials: T
authors.lastname: Gerlach
authors.forename: Helmut
authors.initials: H
authors.lastname: Diepolder
authors.forename: Carl-Albrecht
authors.initials: CA
authors.lastname: Schirren
authors.forename: Mark
authors.initials: M
authors.lastname: Page
authors.forename: John
authors.initials: J
authors.lastname: Bailey
authors.forename: Emma
authors.initials: E
authors.lastname: Birtles
authors.forename: Eve
authors.initials: E
authors.lastname: Whitehead
authors.forename: Jörg
authors.initials: J
authors.lastname: Trojan
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Pape
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D007376:Interleukin-2; D015848:Interleukin-5; D016753:Interleukin-10; D007371:Interferon-gamma; D000410:Alanine Transaminase