Topical resiquimod promotes priming of CTL to parenteral antigens

Vaccine. 2009 Sep 25;27(42):5791-9. doi: 10.1016/j.vaccine.2009.07.062. Epub 2009 Aug 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology*
  • Administration, Cutaneous
  • Animals
  • Cross-Priming / immunology*
  • Cytokines / immunology
  • Female
  • Imidazoles / pharmacology*
  • Immunity, Cellular
  • Injections, Subcutaneous
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic / drug effects*
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 8 / agonists


  • Adjuvants, Immunologic
  • Cytokines
  • Imidazoles
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • resiquimod