title: Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections.
abstract: Although DNA vaccines represent an attractive approach for generating antigen-specific immunity, improvement of their potency is highly demanded. In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections. We found that C57BL/6 immunization with E7-NT-gp96 fusion gene led to increased level of IFN-γ compared to E7 alone. The fused genes showed considerable protective potency in tumor mice model. In addition, E7-NT-gp96 delivered with PEI600-Tat was more protective against E7-expressing tumors comparing with E7-NT-gp96 alone. Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery. Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth. The successful treatment by this immunization protocol was associated with the elevated levels of IFN-γ and IL-2 production in the lymph nodes. These data indicated that fusion of NT-gp96 to E7 in combination with IP-10 co-administration and PEI600-Tat delivery system can synergistically enhance the potency of HPV DNA vaccines. Therefore, this approach suggests a combinational therapeutic strategy against cervical and other HPV-related cancers.
authors.affiliation: Molecular Immunology and Vaccine Research Lab., Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Mohit
authors.forename: Azam
authors.initials: A
authors.lastname: Bolhassani
authors.forename: Farnaz
authors.initials: F
authors.lastname: Zahedifard
authors.forename: Negar
authors.initials: N
authors.lastname: Seyed
authors.forename: Ali
authors.initials: A
authors.lastname: Eslamifar
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taghikhani
authors.forename: Katayoun
authors.initials: K
authors.lastname: Samimi-Rad
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D054357:Chemokine CXCL10 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015696:Gene Products, tat / Q000494:pharmacology; D018014:Gene Transfer Techniques; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology; D056747:Immunomodulation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000517:prevention & control / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000276:immunology / Q000494:pharmacology; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D011094:Polyethyleneimine / Q000494:pharmacology; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D015696:Gene Products, tat; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; C053387:endoplasmin; D011094:Polyethyleneimine