title: Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver.
abstract: The prevalence of hepatitis B virus (HBV) infection in Asia and sub-Sahara Africa is alarming. With quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, the need for a prophylactic or therapeutic vaccination approach that can effectively induce protective responses against the different genotypes of HBV is more important than ever. Such a strategy will require both the induction of a strong antigen-specific immune response and the subsequent deployment of immune response towards the liver. Here, we assessed the ability of a synthetic DNA vaccine encoding a recombinant consensus plasmid from genotype A through E of the HBV core antigen (HBcAg), to drive immunity in the liver. Intramuscular vaccination induced both strong antigen-specific T cell and high titer antibody responses systematically and in the liver. Furthermore, immunized mice showed strong cytotoxic responses that eliminate adoptively transferred HBV-coated target cells. Importantly, vaccine-induced immune responses provided protection from HBcAg plasmid-based liver transfection in a hydrodynamic liver transfection model. These data provide important insight into the generation of peripheral immune responses that are recruited to the liver-an approach that can be beneficial in the search for vaccines or immune-therapies to liver disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: N
authors.initials: N
authors.lastname: Obeng-Adjei
authors.forename: D K
authors.initials: DK
authors.lastname: Choo
authors.forename: J
authors.initials: J
authors.lastname: Saini
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: P
authors.initials: P
authors.lastname: Pankhong
authors.forename: A
authors.initials: A
authors.lastname: Parikh
authors.forename: J S
authors.initials: JS
authors.lastname: Chu
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005814:Genes, Viral; D005838:Genotype; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy; D006512:Hepatitis B Core Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology / Q000821:virology; D008099:Liver / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000378:metabolism; D014162:Transfection; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA