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Vaccine Adjuvants
Additives in vaccines that enhance immune response that significantly increase vaccine efficacy [1,2]
May cause inflammatory side effects, such as pyrexia, which limits their use [2]
Toll-Like Receptors-7 and -8 and Imidazoquinolines
Endosomally localized TLR-7/8 play a role in the activation of immune cells in humans [3]
TLR-7/8 agonists, including imidazoquinolines, trigger the secretion of proinflammatory cytokines via the NF-κB signaling pathway [1,4]
Unconjugated small molecule imidazoquinolines, such as imiquimod (IMQ) and resiquimod (R848), administered intramuscularly or subcutaneously are prone to diffuse away from the injection site or enter the bloodstream rapidly due to their low molecular weight, resulting in systemic toxicity and flu-like symptoms [5-7]
Topical application of IMQ, approved by the FDA [5], and R848 may induce strong local and systemic inflammatory reactions [7]
Thermoresponsive Polymers
Aggregate at their lower critical solution temperature (LCST) (Figure 1)
Phase transition is reversible and therefore beneficial in cases of adverse reactions to vaccines
LCST of pNIPAM can be engineered to occur sharply within physiological temperatures [2]
Figure 1. (a) A representation of a thermoresponsive polymer undergoing the transition of coil structure to globule structure at the lower critical solution temperature (LCST). (b) This study produces a thermophobic imidazoquinoline-based TLR-7/8 agonist polymer vaccine adjuvant that assembles into nanoparticles that decrease in size and immunogenicity in response to temperature.
Research Question
Will conjugating a TLR-7/8 agonist to a thermoresponsive polymer modulate TLR-mediated immunogenicity?
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