Cai Jianzhou, Zhang Wu, Xu Jiake, Xue Wei, Liu Zonghua
1 Department of Biomedical Engineering, Jinan University, Guangzhou, China.
2 Department of Stomatology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
J Biomater Appl. 2017 Nov;32(5):677-685. doi: 10.1177/0885328217735221. Epub 2017 Oct 9.
Chitosan, as a potential vaccine delivery material, has obtained much attention for immunization prevention and therapy. However, its poor water solubility brings inconvenience for the practical applications. To address this issue, researchers have carried out many chemical modifications to prepare water-soluble chitosan derivatives for vaccine delivery. In this work, we prepared a chitosan derivative N-phosphonium chitosan with excellent water solubility and explored its potential as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. Different vaccine formulations were intramuscularly injected into test mice. Through an immunohistochemistry assay, N-phosphonium chitosan-based antigen formulation could promote antigen arrival from injection site to the secondary lymph organ spleen. Further immunization results showed that 1 mg/ml N-phosphonium chitosan-based vaccine formulation could contribute to significantly higher level of antigen-specific immune responses, including higher antigen-specific IgG antibody titer, splenocyte proliferation, and cytokines secretion (interferon-γ, interleukin-10, and interleukin-4) by the splenocytes of the immunized mice. From the results, the water-soluble chitosan derivative N-phosphonium chitosan could be developed as a potential antigen carrier for immunization prevention and therapy.
壳聚糖作为一种潜在的疫苗递送材料，在免疫预防和治疗方面已受到广泛关注。然而，其较差的水溶性给实际应用带来了不便。为了解决这个问题，研究人员进行了许多化学修饰以制备用于疫苗递送的水溶性壳聚糖衍生物。在这项工作中，我们制备了具有优异水溶性的壳聚糖衍生物N-膦酰基壳聚糖，并以卵清蛋白作为模型抗原，探索了其作为肌肉注射疫苗递送系统的潜力。将不同的疫苗制剂肌肉注射到实验小鼠体内。通过免疫组织化学分析，基于N-膦酰基壳聚糖的抗原制剂可促进抗原从注射部位到达二级淋巴器官脾脏。进一步的免疫结果表明，1mg/ml基于N-膦酰基壳聚糖的疫苗制剂可显著促进更高水平的抗原特异性免疫反应，包括更高的抗原特异性IgG抗体滴度、脾细胞增殖以及免疫小鼠脾细胞分泌细胞因子（干扰素-γ、白细胞介素-10和白细胞介素-4）。从结果来看，水溶性壳聚糖衍生物N-膦酰基壳聚糖可被开发为一种潜在的用于免疫预防和治疗的抗原载体。
