Topical resiquimod promotes priming of CTL to parenteral antigens.
We explored the topical use of resiquimod (R-848), a Toll-like receptor (TLR) 7/8 agonist, in gel formulation, to enhance cross-priming to subcutaneously administered protein antigen in a murine model. Resiquimod application at the time of subcutaneous administration of ovalbumin generated robust antigen-specific CTL as detected by tetramers, IFN-gamma ELISPOT assays and standard cytotoxicity assays. Induced CTL were capable of mediating antigen-specific killing in vivo as measured by in vivo cytotoxicity assays and an ability to protect against B16-OVA tumor challenge. Multiple serial applications of topical resiquimod increased the frequency of antigen-specific CTL when compared to single application. This enhanced frequency was noted despite a marked inhibition of adjuvant mediated pro-inflammatory cytokine release following repeated administration. Topical resiquimod is a potent adjuvant for locally administered subcutaneous vaccines, inducing clinically relevant CTL responses following single application at the time of subcutaneous vaccination.
Chang
Brent A
BA
Child and Family Research Institute, Department of Dermatology & Skin Science, University of British Columbia, 835 West Tenth Ave, Vancouver, BC, Canada V5Z 4E8.
Cross
Jennifer L
JL
Najar
Hossain M
HM
Dutz
Jan P
JP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D045142:Cross-Priming / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D007111:Immunity, Cellular; D007279:Injections, Subcutaneous; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051200:Toll-Like Receptor 8 / Q000819:agonists
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007093:Imidazoles; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C402365:resiquimod