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

• Published in: Carbohydrate polymers Vol. 236; p. 116041
• Main Authors: Tsai, Meng-hung, Chuang, Chuan-chang, Chen, Cheng-cheung, Yen, Hui-ju, Cheng, Kuang-ming, Chen, Xin-an, Shyu, Huey-fen, Lee, Chia-ying, Young, Jenn-jong, Kau, Jyh-hwa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.05.2020
• Subjects: Anthrax vaccine; anthrax vaccines; antibodies; Cellular uptake; Cytokines; Cytotoxicity; electrolytes; flow cytometry; fluorescence microscopes; fucoidan; Fucoidan-trimethylchitosan nanoparticles; humoral immunity; Immune protection; Immune response; immunoglobulin G; interleukin-12; interleukin-4; nanoparticles; oligodeoxyribonucleotides; vaccine adjuvants; viability; Fucoidan-trimethylchitosan nanoparticles; Cellular uptake; Immune response; Cytokines; Anthrax vaccine; Immune protection; Cytotoxicity
• ISSN: 0144-8617; 1879-1344; 1879-1344
• DOI: 10.1016/j.carbpol.2020.116041

•Positively or negatively surface-charged FUC-TMC NPs were prepared via PEC method.•Both charged NPs showed high cell viability and low cytotoxicity on L929 cell and DC.•Both charged FUC-TMC NPs deliver drugs into the cytoplasm and the nucleus.•NPs enhanced both cellular and humoral immunity, and dominated in humoral immunity.•AVA plus NPs show 100 % A/J mice survival rate when challenged with B. anthrax spore. 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 pro-inflammatory cytokines IFN-γ, 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.