Immunomodulators identified via high-throughput screening enhance control of vaccine adjuvanticity

Abstract Stimulation of the innate immune system is crucial in both vaccinations and immunotherapies. This often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) stimulate two signaling pathways: nuclear factor kappa-light-chain-enhancer activated B-cells pathway (NF-κB) interferon regulatory factors (IRF). Engineering response via fine control these pathways, however, quite difficult. We demonstrate ability to alter improve adjuvant activity addition small molecule “immunomodulators” existing PRR agonists. By modulating instead receptor binding, allow customization select responses. inhibition enhancement products NF-κB IRF pathways by several orders magnitude. Some modulators apply generally across many receptors, while others focus specifically on individual receptors. Modulators boosted correlates a protective responses an inactivated flu vaccine reduced reactogenicity subunit typhoid vaccine. These have range applications: from adjuvanticity prophylactics immunotherapy. approach offers greater over early activation provides researchers with new tool tailor end NIH 75N93019C00041