title: Improving on the ability of endogenous hepatitis B core antigen to prime cytotoxic T lymphocytes.
abstract: Hepatitis B virus core antigen (HBcAg) is thought to be a major target for specific cytotoxic T cells (CTLs) in hepatitis B virus infections. A single dose of hepatitis C virus nonstructural 3/4A DNA (<5 microg) effectively primes functional specific CTLs, independently of CD4(+) T helper cells and by different routes of immunization. In contrast, HBcAg-specific CTL priming was T helper cell dependent and highly sensitive to the dose and route of delivery. Although CTL priming was improved 10-fold by codon optimization and in vivo electroporation, low levels of DNA still failed to prime CTLs effectively. Only high doses (5 microg) of codon-optimized HBcAg delivered by in vivo electroporation primed in vivo lytic and polyfunctional CTLs. The ability of endogenous HBcAg to prime CTLs is surprisingly inefficient and differs from that of nonstructural 3/4A. This has important implications for the design of HBcAg-based therapeutic vaccines in humans.
authors.affiliation: Division of Clinical Microbiology, of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Nyström
authors.forename: Antony
authors.initials: A
authors.lastname: Chen
authors.forename: Lars
authors.initials: L
authors.lastname: Frelin
authors.forename: Gustaf
authors.initials: G
authors.lastname: Ahlén
authors.forename: Sarene
authors.initials: S
authors.lastname: Koh
authors.forename: Anette
authors.initials: A
authors.lastname: Brass
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Peterson
authors.forename: Michael
authors.initials: M
authors.lastname: Fons
authors.forename: David R
authors.initials: DR
authors.lastname: Milich
authors.forename: Catharina
authors.initials: C
authors.lastname: Hultgren
authors.forename: Matti
authors.initials: M
authors.lastname: Sällberg
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018274:Electroporation; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus