Journal Article

Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs

Bahmani, Azadeh, Esser-Kahn, Aaron P., Kim, Jeremiah Y., Shen, Jinjing, Wang, Andrew, IP, Carman KM, Chen, Siquan, Rosenberger, Matthew G., Kenna, Emma, Tay, Savaş, Ferguson, Andrew L., Son, Minjun, Tang, Yifeng, Chen, Qing

2023

Overview

Stimulation of the innate immune system is crucial in both effective vaccinations and immunotherapies. This is often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) and stimulate two innate immune signaling pathways: the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway (NF-κB) and the interferon regulatory factors pathway (IRF). Here, we demonstrate the ability to alter and improve adjuvant activity via the addition of small molecule “immunomodulators”. By modulating signaling activity instead of receptor binding, these molecules allow the customization of select innate responses. We demonstrate both inhibition and enhancement of the products of the NF-κB and IRF pathways by several orders of magnitude. Some modulators apply generally across many receptors, while others focus specifically on individual receptors. Modulators boost correlates of a protective immune responses in a commercial flu vaccine model and reduced correlates of reactogenicity in a typhoid vaccine model. These modulators have a range of applications: from adjuvanticity in prophylactics to enhancement of immunotherapy.

• Publisher: American Chemical Society
• Subject: Adjuvanticity / Adjuvants / Antibodies / Antigens / Cytokines / FDA approval / High-throughput screening / Immune response / Immune system / Immunomodulation / Immunomodulators / Immunotherapy / Innate immunity / Libraries / Lymphocytes B / NF-κB protein / Pattern recognition / Pattern recognition receptors / Receptors / Signal transduction / Transcription factors / Trends / Typhoid / Vaccines