TLR-Based Adjuvant Development in Non-Human Primates

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The innate immune system is essential for the immediate response to infectious challenge. It is now apparent that Toll-like receptors (TLR) are key in mediating this response by the recognition of ligands expressed by a wide variety of infectious agents. It has been demonstrated in mouse models that stimulation of the innate immune system by TLR ligands results in a transiently heightened nonspecific state of resistance to some infections. Furthermore, activation of the innate immune system by the use of adjuvants during vaccination is necessary for the development of an antigen-specific immune response. However, the identity of the antigen presenting cell (or cells) as well as the exact signals that are delivered to those cells by adjuvants are unknown. Species-specific differences in the expression pattern of TLRs as well as in the ligands recognized by specific TLRs have been demonstrated, suggesting that primate models may be more predictive of human responses than mouse models in response to TLR ligands. We therefore propose to carefully dissect the activation of various ARC populations by defined TLR ligands in vitro and to examine effector responses generated to model antigens combined with specific TLR ligands in vivo.