title: Comparing the effect of Toll-like receptor agonist adjuvants on the efficiency of a DNA vaccine.
abstract: We have investigated whether poly(I:C) Toll-like receptor 3 (TLR3) and resiquimod Toll-like receptor 7 (TLR7) agonists can serve as vaccine adjuvants and promote the efficiency of therapeutic DNA vaccination against tumors expressing the human papilloma virus 16 (HPV-16) E7 protein. For this purpose, C57BL/6 mice were inoculated with 2 × 10(5) TC-1 cells, and they were then immunized with HPV-16 E7 DNA vaccine alone or with 50 μg of resiquimod or poly(I:C) individually. We found that poly(I:C) and resiquimod could induce more antigen-specific lymphocyte proliferation and cytolytic activity compared to vaccination with E7 DNA alone. While E7 DNA had no significant inhibitory effect on tumor growth, co-administration of poly(I:C) and resiquimod with E7 DNA induced significant tumor regression. Peripheral and local cytokine assays demonstrated that co-administration of poly(I:C) and resiquimod with E7 DNA induced circulating antigen-specific IFN-γ and nonspecific intratumoral IL-12. TLR3 and TLR7 agonists can be used to enhance the immune response to DNA vaccine immunogens. Taken together, these data indicate that combined vaccination with DNA encoding HPV-16 E7 plus TLR agonists provides a strategy for improving the efficacy of a vaccine as a possible immunotherapeutic strategy for cervical cancer.
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Sajadian
authors.forename: Alijan
authors.initials: A
authors.lastname: Tabarraei
authors.forename: Hoorieh
authors.initials: H
authors.lastname: Soleimanjahi
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Fotouhi
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
authors.forename: Amir
authors.initials: A
authors.lastname: Ghaemi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16