Immunostimulatory DNA containing unmethylated CpG motifs is recognized by Toll-like receptor 9, resulting in the activation of innate immune responses that subsequently amplify the adaptive-immune response. Advances in the characterization of Toll-like receptor 9 signaling have identified immunostimulatory sequences (ISS) with distinct biological activities. Numerous animal models have demonstrated that synthetic ISS are effective adjuvants that enhance both humoral and cellular immune responses in diverse indications, ranging from infectious disease to cancer and allergy. An added benefit supporting the use of ISS as a vaccine adjuvant is that the specific activation of a pathway critical to the regulation of the immune response results in minimal toxicity. To date, clinical testing has largely affirmed the potency and safety of ISS-adjuvanted vaccines.
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Higgins et al. (2007) studied this question.
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