期刊
JOURNAL OF CONTROLLED RELEASE
卷 214, 期 -, 页码 12-22出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2015.07.008
关键词
Liquid crystal; Ascorbyl palmitate; Nanostructure; Controlled release; Vaccine adjuvant; Danger-associated molecular patterns (DAMPs)
资金
- Agencia Nacional de Promocion Cientifica y Tecnica (PICT-MICINN) [2772]
- Secretaria de Ciencia y Tecnica de la Universidad Nacional de Cordoba
- Ministerio de Ciencia y Tecnologia de la Provincia de Cordoba (PID)
- CONICET [11220090100109]
- Ministerio de Ciencia e Innovacion [PRI-PIBAR-2011-1397]
- Ministerio de Economia y Competitividad [SAF 2012-35670]
- CONICET
- Agencia Nacional de Promocion Cientifica y Tecnica
Modern subunit vaccines require the development of new adjuvant strategies. Recently, we showed that CpG-ODN formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system for promoting an antigen-specific immune response to weak antigens. Here, we showed that after subcutaneous injection of mice with near-infrared fluorescent dye-labeled OVA antigen formulated with Coa-ASC16, the dye-OVA was retained at the injection site for a longer period than when soluble dye-OVA was administered. Coa-ASC16 alone elicited a local inflammation, but how this material triggers this response has not been described yet. Although it is known that some materials used as a platform are not immunologically inert, very few studies have directly focused on this topic. In this study, we explored the underlying mechanisms concerning the interaction between Coa-ASC16 and the immune system and we found that the whole inflammatory response elicited by Coa-ASC16 (leukocyte recruitment and IL-1 beta, IL-6 and IL-12 production) was dependent on the MyD88 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling were not required for induction of this inflammatory response. Coa-ASC16 induced local release of self-DNA, and in TLR9-deficient mice IL-6 production was absent. In addition, Coa-ASC16 revealed an intrinsic adjuvant activity which was affected by MyD88 and IL-6 absence. Taken together these results indicate that Coa-ASC16 used as a vaccine platform is effective due to the combination of the controlled release of antigen and its intrinsic pro-inflammatory activity. Understanding how Coa-ASC16 works might have significant implications for rational vaccine design. (C) 2015 Elsevier B.V. All rights reserved.
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