Developing a Targeted Adjuvant using Polymeric Micelles and Resiquimod
Resiquimod (R848) is an adjuvant that amplifies the immune response through the activation of the intracellular toll-like receptors (TLRs) 7 and 8. Adjuvants make immune responses to vaccines stronger and broader, improving vaccine efficacy. The TLR7/8 pathways activates the innate immune response, providing immediate immunity and releasing signals that enact fast recruitment of additional innate and adaptive immune cells, resulting in both a broad and specific response. TLR7/8 receptors are intracellular receptors in endosomes and delivery of R848, a poorly soluble small molecule, to endosomes will be unsuccessful alone. The use of a lipid nanoparticle is advantageous for uptake through lymph and into endosomes, where it can then be degraded and R848 can bind to TLR7 or 8. Dose response studies in a human embryonic kidney cell line (HEK293) with TLR7/8 receptors showed increased activation in response to R848. Encapsulation of R848 in PA11 increased intracellular uptake and TLR7 activation, however there was no clear correlation between R848 concentration in PA11 and TLR7 activation.