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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

Authors
 Chanyoung Song  ;  #1  ;  * Hathaichanok Phuengkham  ;  #1  ;  * Sun-Young Kim  ;  1 Min Sang Lee  ;  2 Ji Hoon Jeong  ;  2 Sung Jae Shin  ;  3 and Yong Taik Lim 
Citation
 International Journal of Nanomedicine, Vol.12 : 7501-7517, 2017 
Journal Title
 International Journal of Nanomedicine 
ISSN
 1176-9114 
Issue Date
2017
MeSH
Adjuvants, Immunologic/pharmacology* ; Amines/chemistry* ; Animals ; Caspase 1/metabolism ; Female ; Immunity, Innate*/drug effects ; Inflammasomes/metabolism* ; Lymph Nodes/drug effects ; Lymph Nodes/immunology* ; Mice, Inbred C57BL ; Mice, Knockout ; Micelles* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nanoparticles/chemistry* ; Poly I-C/pharmacology ; Polyglutamic Acid/analogs & derivatives ; Polyglutamic Acid/chemistry ; Vaccines/immunology*
Abstract
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/161440
DOI
10.2147/IJN.S144623
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실)
Yonsei Authors
신성재(Shin, Sung Jae)
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