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

[Image: see text] 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 fact...

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Autores principales: Kim, Jeremiah Y., Rosenberger, Matthew G., Chen, Siquan, IP, Carman KM, Bahmani, Azadeh, Chen, Qing, Shen, Jinjing, Tang, Yifeng, Wang, Andrew, Kenna, Emma, Son, Minjun, Tay, Savaş, Ferguson, Andrew L., Esser-Kahn, Aaron P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037445/
https://www.ncbi.nlm.nih.gov/pubmed/36968540
http://dx.doi.org/10.1021/acscentsci.2c01351
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author Kim, Jeremiah Y.
Rosenberger, Matthew G.
Chen, Siquan
IP, Carman KM
Bahmani, Azadeh
Chen, Qing
Shen, Jinjing
Tang, Yifeng
Wang, Andrew
Kenna, Emma
Son, Minjun
Tay, Savaş
Ferguson, Andrew L.
Esser-Kahn, Aaron P.
author_facet Kim, Jeremiah Y.
Rosenberger, Matthew G.
Chen, Siquan
IP, Carman KM
Bahmani, Azadeh
Chen, Qing
Shen, Jinjing
Tang, Yifeng
Wang, Andrew
Kenna, Emma
Son, Minjun
Tay, Savaş
Ferguson, Andrew L.
Esser-Kahn, Aaron P.
author_sort Kim, Jeremiah Y.
collection PubMed
description [Image: see text] 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.
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spelling pubmed-100374452023-03-25 Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs Kim, Jeremiah Y. Rosenberger, Matthew G. Chen, Siquan IP, Carman KM Bahmani, Azadeh Chen, Qing Shen, Jinjing Tang, Yifeng Wang, Andrew Kenna, Emma Son, Minjun Tay, Savaş Ferguson, Andrew L. Esser-Kahn, Aaron P. ACS Cent Sci [Image: see text] 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. American Chemical Society 2023-02-23 /pmc/articles/PMC10037445/ /pubmed/36968540 http://dx.doi.org/10.1021/acscentsci.2c01351 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Kim, Jeremiah Y.
Rosenberger, Matthew G.
Chen, Siquan
IP, Carman KM
Bahmani, Azadeh
Chen, Qing
Shen, Jinjing
Tang, Yifeng
Wang, Andrew
Kenna, Emma
Son, Minjun
Tay, Savaş
Ferguson, Andrew L.
Esser-Kahn, Aaron P.
Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs
title Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs
title_full Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs
title_fullStr Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs
title_full_unstemmed Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs
title_short Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs
title_sort discovery of new states of immunomodulation for vaccine adjuvants via high throughput screening: expanding innate responses to prrs
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037445/
https://www.ncbi.nlm.nih.gov/pubmed/36968540
http://dx.doi.org/10.1021/acscentsci.2c01351
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