Pritzker School of Molecular Engineering
Published February 23, 2023 | Version v1
Journal article Open

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

Creators

  • 1. University of Chicago

Description

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.

Files

kim-et-al-2023-discovery-of-new-states-of-immunomodulation-for-vaccine-adjuvants-via-high-throughput-screening.pdf

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Additional details

Identifiers

DOI
10.1021/acscentsci.2c01351
Other
oai:uchicago.tind.io:13409

Funding

National Institute of Allergy and Infectious Diseases
NIH 75N93019C00041

UChicago Information

Division(s)
Pritzker School of Molecular Engineering