Topical resiquimod promotes priming of CTL to parenteral antigens

• DOI: 10.1016/j.vaccine.2009.07.062
• Publication Date: 2009-08-05T09:20:28Z
• Authors: Brent A. Chang; Jennifer L. Cross; Hossain M. Najar; Jan P. Dutz
• Keywords: 0301 basic medicine; Immunity, Cellular; Injections, Subcutaneous; Imidazoles; Melanoma, Experimental; Administration, Cutaneous; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cross-Priming; Adjuvants, Immunologic; Toll-Like Receptor 7; Toll-Like Receptor 8; Animals; Cytokines; Female; T-Lymphocytes, Cytotoxic

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.