Int J Pharm. 2018 Sep 19. pii: S0378-5173(18)30703-8. doi: 10.1016/j.ijpharm.2018.09.044. [Epub ahead of print]
Mechanistic study of the adjuvant effect of chitosan-aluminum nanoparticles.
Lebre F1, de Lima MCP2, Lavelle EC3, Borges O4.
Author information
1
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, Universityof Coimbra, Pólo das Ciências da Saúde Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02 PN40, Ireland; Advanced Materials Bio-Engineering Research Centre (AMBER), Trinity College Dublin, Dublin 2 D02 PN40, Ireland.
2
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
3
Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02 PN40, Ireland; Advanced Materials Bio-Engineering Research Centre (AMBER), Trinity College Dublin, Dublin 2 D02 PN40, Ireland.
4
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, Universityof Coimbra, Pólo das Ciências da Saúde Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal. Electronic address: [email protected].
Abstract
The use of tailored particle-based adjuvants constitutes a promising way to enhance antigen-specific humoral and cellular immune responses. However, a thorough understanding of the mechanisms underlying their adjuvanticity is crucial to generate more effective vaccines. We studied the ability of chitosan-aluminum nanoparticles (CH-Al NPs), which combine the immunostimulatory effects of chitosan and aluminum salts, to promote dendritic cell activation, assess their impact on innate and adaptive immune responses and compare the results to those reported for conventional chitosan particles (CH-Na NPs). All tested CH-NP formulations were capable of modulating cytokine secretion by dendritic cells. CH-Al NPs promoted NLRP3 inflammasome activation, enhancing the release of IL-1β without significantly inhibiting Th1 and Th17 cell- polarizing cytokines, IL-12p70 or IL-23, and induced DC maturation, but did not promote pro-inflammatory cytokine production on their own. In vivo results showed that mice injected with CH-Al NPs generated a local inflammatory response comparable to that elicited by the vaccine adjuvant alum. Importantly, after subcutaneous immunization with CH-Al NPs combined with the hepatitis B surface antigen (HBsAg), mice developed antigen-specific IgG titers in serum, nasal and vaginal washes. Overall, our results established CH-Al NPs as a potential adjuvant to enhance both innate and adaptive immune responses.
KEYWORDS:
Adaptive immunity; Adjuvant; Chitosan nanoparticles; Hepatitis B vaccine; Innate immunity
PMID:
30244149
DOI:
10.1016/j.ijpharm.2018.09.044
作者: StephenW 时间: 2018-9-25 10:22
Int J Pharm。 2018年9月19日.pii：S0378-5173（18）30703-8。 doi：10.1016 / j.ijpharm.2018.09.044。 [提前打印]
壳聚糖 - 铝纳米粒子佐剂效应的机理研究。
Lebre F1，de Lima MCP2，Lavelle EC3，Borges O4。
作者信息