Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering , Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300192 , P. R. China.
Department of Biomedical Engineering , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
ACS Appl Mater Interfaces. 2018 Jul 5;10(26):21861-21875. doi: 10.1021/acsami.8b04867. Epub 2018 Jun 25.
Combined nanovaccine can generate robust and persistent antigen-specific immune responses. A combined nanovaccine was developed based on antigen-loaded genipin-cross-linked-polyethyleneimine-antigen nanoparticles and in vivo multispectral fluorescence imaging tracked the antigen delivery of combined nanovaccine. The inner layer antigen nanoparticles carried abundant antigens by self-cross-linking for persistent immune response, whereas the outer antigen on the surface of antigen nanoparticles provided the initial antigen exposure. The delivery of combined nanovaccine was tracked dynamically and objectively by the separation of inner genipin cross-linked antigen nanoparticle and the outer fluorescent antigen. The immune responses of the combined nanovaccine were evaluated including antigen-specific CD4 and CD8 T-cell responses, IgG antibody level, immunological memory, and CD8 cytotoxic T lymphocyte responses. The results indicated that the inner and outer antigens of combined vaccine can be tracked in real time with a programmed delivery by the dual fluorescence imaging. The programmed delivery of the inner and outer antigens induced strong immune responses with a combination of a quick delivery and a persistent delivery. With adequate antigen exposure, the dendritic cells were effectively activated and matured, and following T cells were further activated for immune response. Compared with a single nanoparticle formulation, the combined nanovaccine exactly elicited a stronger antigen-specific immune response.
联合纳米疫苗可产生强大且持久的抗原特异性免疫应答。基于载抗原的京尼平交联聚亚胺-抗原纳米颗粒和体内多光谱荧光成像，开发了联合纳米疫苗。内层抗原纳米颗粒通过自交联携带丰富的抗原以产生持久的免疫应答，而抗原纳米颗粒表面的外层抗原则提供初始抗原暴露。通过内源性京尼平交联抗原纳米颗粒和外源性荧光抗原的分离，动态和客观地跟踪了联合纳米疫苗的递呈。评估了联合纳米疫苗的免疫应答，包括抗原特异性 CD4 和 CD8 T 细胞应答、IgG 抗体水平、免疫记忆和 CD8 细胞毒性 T 淋巴细胞应答。结果表明，双荧光成像可实时跟踪联合疫苗的内、外抗原的程序化递呈。内、外抗原的程序化递呈通过快速递呈和持续递呈相结合，诱导强烈的免疫应答。通过充分的抗原暴露，树突状细胞被有效激活和成熟，随后 T 细胞被进一步激活以产生免疫应答。与单一纳米颗粒制剂相比，联合纳米疫苗确实引发了更强的抗原特异性免疫应答。
