Chitosan hydrogel loaded with recombinant protein containing epitope C from HSP90 of Candida albicans induces protective immune responses against systemic candidiasis
2021
Li, Xiaozhou | Yang, Ye | Yang, Fan | Wang, Feihe | Li, Hong | Tian, Huayu | Wang, Guiyun
We reported previously a recombinant protein (rP-HSP90C) containing epitope C from heat shock protein 90 of Candida albicans mediates protective immune responses against systemic candidiasis. However, it exhibits weak immunogenicity. Therefore, we evaluated the potential and mechanisms of thermosensitive chitosan hydrogel (CH-HG) as an adjuvant in rP-HSP90C vaccine. CH-HG synthesized by ionic cross-linking showed buffering capacity and control-released rP-HSP90C in vitro. In comparison to naked rP-HSP90C, CH-HG-loaded rP-HSP90C (CH-HG/rP-HSP90C) not only evoked a long-lasting rP-HSP90C-specific IgG, but also enhanced Th1, Th2, Th17 responses and the ratio of Th1/Th2 in vivo; Meanwhile, CH-HG/rP-HSP90C provoked a stronger CTL response than rP-HSP90C. Notably, CH-HG increased the protective immune responses against systemic candidiasis in rP-HSP90C-immunized mice since CH-HG/rP-HSP90C enhanced the survival rate of infected mice, and diminished the CFUs in kidneys compared to rP-HSP90C, which were similar to that of QuilA. Further in vitro investigation displayed CH-HG upgraded the expressions of costimulators, MHCs and cytokines in BMDCs compared to rP-HSP90C；CH-HG also promoted cellular uptake, endosomal escape and “cross-presentation” of rP-HSP90C. In addition, it recruited immune cells at the injection site. Our study demonstrated that CH-HG can be an efficient adjuvant in fungal vaccines.
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