The toll-like receptors are antigen-recognition receptors for innate immunity. They recognize pathogen components and trigger innate immune responses that in turn activate the adaptive immune system. Of the 12 TLRs, the most widely used as targets for agonists are TLR3, TLR7/8 and TLR9. TLR4 antagonists are in development for septic shock conditions with leads in phase III . TLR7/8/9 antagonists are pursued for to treat systemic lupus erythematosus (SLE) with a lead compound in phase I. Imiquimod is the first marketed TLR agonist for topical treatment of genitoanal warts, basal cell carcinomas and actinic keratosis. Of the 15 clinical stage TLR agonists, ten are directed against TLR9 with further five TLR9 agonists to enter shortly phase I. Main indications for TLR9 agonists are cancer and pulmonary & respiratory diseases such as asthma, COPD and allergic rhinitis. The use of TLR agonists as adjuvants with vaccines confers the great advantage to accelerate the immune response, e.g. two instead of three doses, and allow dose reduction. At least 12 different TLR agonists are used or evaluated as vaccine adjuvants. Marketed vaccines using a TLR4 agonist as adjuvant in prophylactic vaccines are Fendrix and Cervarix from GlaxoSmithKline. TLR agonists are also used in therapeutic vaccines to treat cancer, established infectious diseases and as desensitization in allergic diseases.

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