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Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes

In this study, we suggest a designer vaccine adjuvant that can mimic the drainage of pathogens into lymph nodes and activate innate immune response in lymph nodes. By the amination of multivalent carboxyl groups in poly-(γ-glutamic acid) (γ-PGA) nanomicelles, the size was reduced for rapid entry int...

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Autores principales: Song, Chanyoung, Phuengkham, Hathaichanok, Kim, Sun-Young, Lee, Min Sang, Jeong, Ji Hoon, Shin, Sung Jae, Lim, Yong Taik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644533/
https://www.ncbi.nlm.nih.gov/pubmed/29066896
http://dx.doi.org/10.2147/IJN.S144623
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author Song, Chanyoung
Phuengkham, Hathaichanok
Kim, Sun-Young
Lee, Min Sang
Jeong, Ji Hoon
Shin, Sung Jae
Lim, Yong Taik
author_facet Song, Chanyoung
Phuengkham, Hathaichanok
Kim, Sun-Young
Lee, Min Sang
Jeong, Ji Hoon
Shin, Sung Jae
Lim, Yong Taik
author_sort Song, Chanyoung
collection PubMed
description In this study, we suggest a designer vaccine adjuvant that can mimic the drainage of pathogens into lymph nodes and activate innate immune response in lymph nodes. By the amination of multivalent carboxyl groups in poly-(γ-glutamic acid) (γ-PGA) nanomicelles, the size was reduced for rapid entry into lymphatic vessels, and the immunologically inert nanomicelles were turned into potential activators of inflammasomes. Aminated γ-PGA nanomicelles (aPNMs) induced NLRP3 inflammasome activation and the subsequent release of proinflammatory IL-1β. The NLRP3-dependent inflammasome induction mechanism was confirmed through enzyme (cathepsin B and caspase-1) inhibitors and NLRP3 knockout mice model. After the aPNMs were combined with a clinically evaluated TLR3 agonist, polyinosinic–polycytidylic acid sodium salt (aPNM-IC), they triggered multiple arms of the innate immune response, including the secretion of pro-inflammatory cytokines by both inflammasomes and an inflammasome-independent pathway and the included type I interferons.
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spelling pubmed-56445332017-10-24 Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes Song, Chanyoung Phuengkham, Hathaichanok Kim, Sun-Young Lee, Min Sang Jeong, Ji Hoon Shin, Sung Jae Lim, Yong Taik Int J Nanomedicine Original Research In this study, we suggest a designer vaccine adjuvant that can mimic the drainage of pathogens into lymph nodes and activate innate immune response in lymph nodes. By the amination of multivalent carboxyl groups in poly-(γ-glutamic acid) (γ-PGA) nanomicelles, the size was reduced for rapid entry into lymphatic vessels, and the immunologically inert nanomicelles were turned into potential activators of inflammasomes. Aminated γ-PGA nanomicelles (aPNMs) induced NLRP3 inflammasome activation and the subsequent release of proinflammatory IL-1β. The NLRP3-dependent inflammasome induction mechanism was confirmed through enzyme (cathepsin B and caspase-1) inhibitors and NLRP3 knockout mice model. After the aPNMs were combined with a clinically evaluated TLR3 agonist, polyinosinic–polycytidylic acid sodium salt (aPNM-IC), they triggered multiple arms of the innate immune response, including the secretion of pro-inflammatory cytokines by both inflammasomes and an inflammasome-independent pathway and the included type I interferons. Dove Medical Press 2017-10-12 /pmc/articles/PMC5644533/ /pubmed/29066896 http://dx.doi.org/10.2147/IJN.S144623 Text en © 2017 Song et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Song, Chanyoung
Phuengkham, Hathaichanok
Kim, Sun-Young
Lee, Min Sang
Jeong, Ji Hoon
Shin, Sung Jae
Lim, Yong Taik
Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
title Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
title_full Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
title_fullStr Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
title_full_unstemmed Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
title_short Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
title_sort aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644533/
https://www.ncbi.nlm.nih.gov/pubmed/29066896
http://dx.doi.org/10.2147/IJN.S144623
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