title: Design, Immune Responses and Anti-Tumor Potential of an HPV16 E6E7 Multi-Epitope Vaccine.
abstract: Cervical cancer is a common type of cancer among women worldwide and infection with high-risk human papillomavirus (HPVs) types represents the major risk factor for the etiopathogenesis of the disease. HPV-16 is the most frequently identified HPV type in cervical lesions and expression of E6 and E7 oncoproteins is required for the uncontrolled cellular proliferation. In the present study we report the design and experimental testing of a recombinant multi-epitope protein containing immunogenic epitopes of HPV-16 E6 and E7. Tumor preventive assays, based on the engraftment of TC-1 cells in mice, showed that the E6E7 multi-epitope protein induced a full preventive anti-tumor protection in wild-type mice, as well as in mice deficient in expression of CD4+ T cells and TLR4 receptor. Nonetheless, no anti-tumor protection was observed in mice deficient in CD8+ T cells. Also, the vaccine promoted high activation of E6/E7-specific T cells and in a therapeutic-approach, E6E7 protein conferred full anti-tumor protection in mice. These results show a potential use of this E6E7 multi-epitope antigen as a new and promising antigen for the development of a therapeutic vaccine against tumors induced by HPV.
authors.affiliation: Laboratório de Biotecnologia Molecular I, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Liliane Maria Fernandes
authors.initials: LM
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Biotecnologia Molecular I, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Mirian Galliote
authors.initials: MG
authors.lastname: Morale
authors.affiliation: Laboratório de Biotecnologia Molecular I, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Agatha A Muniz
authors.initials: AA
authors.lastname: Chaves
authors.affiliation: Laboratório de Biotecnologia Molecular I, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Aline Marques
authors.initials: AM
authors.lastname: Cavalher
authors.affiliation: Laboratório Especial de Toxinologia Aplicada-CeTICS, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Aline Soriano
authors.initials: AS
authors.lastname: Lopes
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo-SP, Brazil.
authors.forename: Mariana de Oliveira
authors.initials: Mde O
authors.lastname: Diniz
authors.affiliation: Laboratório de Biotecnologia Molecular I, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Alessandra Soares
authors.initials: AS
authors.lastname: Schanoski
authors.affiliation: Laboratório Especial de Toxinologia Aplicada-CeTICS, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Robson Lopes
authors.initials: RL
authors.lastname: de Melo
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo-SP, Brazil.
authors.forename: Luís Carlos de Souza
authors.initials: LC
authors.lastname: Ferreira
authors.affiliation: Laboratório de Biotecnologia Molecular I, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Maria Leonor S
authors.initials: ML
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Marilene
authors.initials: M
authors.lastname: Demasi
authors.affiliation: Laboratório de Biotecnologia Molecular I, Instituto Butantan, Av. Vital Brasil 1500, São Paulo-SP, Brazil.
authors.forename: Paulo Lee
authors.initials: PL
authors.lastname: Ho
mesh_terms: D052685:Alphapapillomavirus / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*
chemical_list: D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D000939:Epitopes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D007371:Interferon-gamma