Modulating vaccine inflammation with thermophobic trehalose glycolipid adjuvant polymers

Abstract Adjuvants drive the efficacy of many vaccines, however, they also elicit undesirable inflammation which is commonly pyrogenic resulting in local or systemic increases temperature. Based on this, we envisioned that inversely coupling adjuvant potency to small (~2 °C) temperature changes could be a uniquely effective approach balance while maintaining safety and tolerability. Here report first Thermophobic Adjuvant Polymers (TAPs) reversibly attenuate response TAPs consisted co-polymers containing both trehalose glycolipid thermoresponsive N-isopropylacrylamide (NIPAM) subunits. In an Influenza A/California/04/2009 virus vaccine mouse model, were adjuvants. Mice immunized with adjuvanted exhibited increased neuraminidase neutralizing antibodies, lymph CD4 +T cells, +/44 +/62L +lung central memory T cells. Protection after viral rechallenge was comparable between alum vaccines. At 37 °C in-vitro, elicited cytokine profiles other adjuvants JAWSII cell line primary CD11c +BMDCs. Relative °C, (TNF-α IL-6) enhanced at 35 abrogated 39 °C. DLS NOESY-NMR suggest temperature-dependent activity due intramolecular hydrophobic shielding NIPAM beyond lower critical solution Overall, this study demonstrates are influenza linked We envision extended enhance Supported by grants from NIH (1R01CA234115), AAI (Careers immunology fellowship), Washington Research Foundation.