title: Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques.
abstract: Human papilloma-virus (HPV) infection is the major cause of cervical cancer. HPV18 is the most prevalent high-risk HPV after type 16 that accounts for the largest number of cervical cancer cases worldwide. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines for targeting tumors post-infection. In this study, we utilize a novel multi-phase strategy for HPV18 antigen development with the goal of increasing anti-HPV18 cellular immunity. Our data show that this construct can induce strong cellular immune responses against HPV18 E6 and E7 antigens in a murine model. Moreover, when applied to rhesus monkeys, this construct is also able to elicit cellular immunity. These data suggest such DNA immunogens are candidates for further study in the eventual context of immunotherapy for HPV-associated cancers.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Kristina
authors.initials: K
authors.lastname: Harris
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Draghia-Akli
authors.forename: Duane
authors.initials: D
authors.lastname: Sewell
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA