4.7 Article

Nanoparticles assembled from fucoidan and trimethylchitosan as anthrax vaccine adjuvant: In vitro and in vivo efficacy in comparison to CpG

期刊

CARBOHYDRATE POLYMERS
卷 236, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2020.116041

关键词

Fucoidan-trimethylchitosan nanoparticles; Cytotoxicity; Cellular uptake; Anthrax vaccine; Immune response; Immune protection; Cytokines

资金

  1. Ministry of Science and Technology [MOST 108-2623-E-016-003-D]
  2. National Defense Medical Center of the Republic of China [MAB-108-071, MAB-108-089, IPM-108-G4, IPM-108-G5]

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Fucoidan/trimethylchitosan nanoparticles (FUC-TMC-NPs) have the potential to improve the immunostimulating efficiency of anthrax vaccine adsorbed (AVA). FUC-TMC-NPs with positive (+) or negative (-) surface charges were prepared via polyelectrolyte complexation, both charged NP types permitted high viability and presented no cytotoxicity on L929, A549 and JAWS II dendritic cells. Flow cytometry measurements indicated lower (+)-FUC-TMC-NPs internalization levels than (-)-FUC-TMC-NPs, yet produced high levels of proinflammatory cytokines IFN-gamma, IL12p40, and IL-4. Moreover, fluorescence microscope images proved that both charged NP could deliver drugs into the nucleus. In vivo studies on A/J mice showed that (+)-FUC-TMC-NPs carrying AVA triggered an efficient response with a higher IgG anti-PA antibody titer than AVA with CpG oligodeoxynucleotides, and yielded 100 % protection when challenged with the anthracis spores. Furthermore, PA-specific IgG1 and IgG2a analysis confirmed that (+)-FUC-TMC-NPs strongly stimulated humoral immunity. In conclusion, (+)-FUC-TMC-NP is promising anthrax vaccine adjuvant as an alternative to CpG.

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