title: A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers.
abstract: The attenuated or non-pathogenic live vectors have been evolved specifically to deliver DNA into cells as efficient delivery tools in gene therapy. Recently, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention. In current study, we used Leishmania expression system (LEXSY) for stable expression of HPV16 E7 linked to different mini-chaperones [N-/C-terminal of gp96] and compared their immunogenicity and protective effects in C57BL/6 mice against TC-1 challenge. TC-1 murine model is primary C57BL/6 mice lung epithelial cells co-transformed with HPV16 E6, HPV16 E7 and ras oncogenes. Our results showed that subcutaneous administration of mice with both the recombinant L.tar-E7-NT (gp96) and L.tar-E7-CT (gp96) led to enhance the levels of IFN-γ and also IgG2a before and after challenge with TC-1. Furthermore, L.tar-E7-CT (gp96) live vaccine indicated significant protective effects as compared to control groups as well as group vaccinated with L.tar-E7. Indeed, the recombinant live vector is capable of eliciting effective humoral and cellular immune responses in mice, but however, further studies are required to increase their efficacy.
authors.affiliation: Molecular Immunology and Vaccine Research Lab., Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Hosseinzadeh
authors.forename: Azam
authors.initials: A
authors.lastname: Bolhassani
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
authors.forename: Tahereh
authors.initials: T
authors.lastname: Taheri
authors.forename: Farnaz
authors.initials: F
authors.lastname: Zahedifard
authors.forename: Amin
authors.initials: A
authors.lastname: Daemi
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Taslimi
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hashemi
authors.forename: Arash
authors.initials: A
authors.lastname: Memarnejadian
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000737:chemistry; D007891:Leishmania / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics / Q000517:prevention & control* / Q000821:virology*; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16