Year: 2023
Type: conference-abstract
Abstract: Adjuvants drive the efficacy of many vaccines, however, they also elicit undesirable inflammation which is commonly pyrogenic resulting in local or systemic increases in temperature. Based on this, we envisioned that inversely coupling adjuvant potency to small (~2 °C) temperature changes could be a uniquely effective approach to balance efficacy while maintaining safety and tolerability. Here we report the first Thermophobic Adjuvant Polymers (TAPs) that reversibly attenuate potency in response to temperature. TAPs consisted of co-polymers containing both trehalose glycolipid adjuvant and thermoresponsive N-isopropylacrylamide (NIPAM) subunits. In an Influenza A/California/04/2009 virus vaccine mouse model, TAPs were effective adjuvants. Mice immunized with TAPs adjuvanted vaccine exhibited increased neuraminidase neutralizing antibodies, lymph CD4+ T cells, and CD4+/44+/62L+ lung central memory T cells. Protection after viral rechallenge was comparable between TAPs and alum adjuvanted vaccines. At 37 °C in-vitro, TAPs elicited cytokine profiles comparable to other glycolipid adjuvants in the JAWSII cell line and primary CD11c+ BMDCs. Relative to 37 °C, inflammation (TNF-α and IL-6) was enhanced at 35 °C and abrogated at 39 °C. DLS and NOESY-NMR suggest that the temperature-dependent activity is due to intramolecular hydrophobic shielding between the adjuvant and NIPAM which is enhanced beyond the lower critical solution temperature. Overall, this study demonstrates TAPs are an effective influenza vaccine adjuvant and elicit inflammation which is inversely linked to temperature. We envision this approach could be extended to many other adjuvants to enhance efficacy while maintaining safety and tolerability. Supported by grants from NIH (1R01CA234115), AAI (Careers in immunology fellowship), and the Washington Research Foundation.
Source: The Journal of Immunology
Institutions: Miami University, Washington State University, Cornell University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4385685952