Modern vaccines, including some SARS-CoV-2, make use of immune-response eliciting agents called adjuvants. While these compounds are effective at stimulating immune responses, they can have varying effects on individuals who receive the vaccine. One instance of these reactions is a high fever or pyrexia leading to safety concerns and in some cases hospitalization. Here we demonstrate the synthesis of a thiol reactive chain transfer agent for use in conjunction with poly-N-isopropylacrylamide (pNIPAM) created by RAFT, a controlled radical polymerization technique for polymerizing monomers. The nonpolar groups and biologically significant Lower Critical Solution Temperature (LCST) of the resulting bioconjugate could allow for the adjuvant to be precipitated out of solution when the body reaches a relatively high temperature. LCST is a property of large molecules that allows them to emmise in solution below a certain temperature, and aggregate when the temperature is exceeded. This property allows for the modulation of the immune response with temperature. It is hypothesized that the thiol reactive polymer can form a disulfide bond with a DNA sequence, encoding an immune response by targeting Toll-like receptor 9. Overall, we hypothesize that the established equilibrium of pNIPAM’s LCST and the rise in temperature during immune response could improve vaccine safety by inversely coupling immune cell activation to pyrexia.

Thermophobic adjuvants targeting toll-like receptor 9 for varying immune response with temperature

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