title: DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques.
abstract: There are well over a quarter of a billion chronic hepatitis B virus (HBV) carriers across the globe. Most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is therefore imperative to develop new approaches for immunotherapy against this infection. Antibodies and cytotoxic T cells to different HBV antigens are believed to be important for reducing viral load and clearing HBV-infected cells from the liver. Some of the major challenges facing current vaccine candidates have been their inability to induce both humoral and cellular immunity to multiple antigenic targets and the induction of potent immune responses against the major genotypes of HBV. In this study, highly optimized synthetic DNA plasmids against the HBV consensus core (HBc) and surface (HBs) antigens genotypes A and C were developed and evaluated for their immune potential. These plasmids, which encode the most prevalent genotypes of the virus, were observed to individually induce binding antibodies to HBs antigens and drove robust cell-mediated immunity in animal models. Similar responses to both HBc and HBs antigens were observed when mice and non-human primates were inoculated with the HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited by the immunized mice, the vaccine-induced responses were broadly distributed across multiple antigenic epitopes. These elements are believed to be important to develop an effective therapeutic vaccine. These data support further evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines.
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: N
authors: N
authors: Obeng-Adjei
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: N A
authors: NA
authors: Hutnick
authors: Inovio Pharmaceuticals Inc., Blue Bell, PA, USA.
authors: J
authors: J
authors: Yan
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: J S
authors: JS
authors: Chu
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: D J F
authors: DJ
authors: Myles
authors: Inovio Pharmaceuticals Inc., Blue Bell, PA, USA.
authors: M P
authors: MP
authors: Morrow
authors: Inovio Pharmaceuticals Inc., Blue Bell, PA, USA.
authors: N Y
authors: NY
authors: Sardesai
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: D B
authors: DB
authors: Weiner
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D023061:Gene Order; D005838:Genotype; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008099:Liver / Q000276:immunology; D008111:Liver Function Tests; D008253:Macaca mulatta; D051379:Mice; D010957:Plasmids / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D019444:Vaccines, DNA