Virus-like particle (VLP) lymphatic trafficking and immune response generation after immunization by different routes.
Virus-like particle (VLP) lymphatic trafficking and immune response generation after immunization by different routes.
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DOI：
10.1097/cji.0b013e31818f13c4
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Yao Q
中科院分区：
文献类型：
--
作者：
Cubas R;Zhang S;Kwon S;Sevick-Muraca EM;Li M;Chen C;Yao Q
病毒样颗粒（VLP）由于其能够有效激活免疫系统的重复性抗原结构而作为疫苗的用途获得了越来越多的兴趣。病毒样颗粒免疫的功效可能在于其运输到引流淋巴结中的能力，同时激活抗原呈递细胞，以启动产生稳健免疫应答所需的信号的协调。目前，还没有全面的研究显示不同VLP疫苗接种途径与免疫结果的相关性。在这项研究中，我们采取了一种光学成像的方法，直接可视化的运输SHIV VLP免疫后，通过常用的路线，并分析相应的体液和细胞免疫反应产生。我们发现VLP可以很容易地进入引流淋巴结的被膜下窦，根据所使用的免疫途径，淋巴结受累的数量存在定量差异。皮内免疫导致最大程度的淋巴结受累持续最长时间，这与最强的体液和细胞免疫应答相关。从提取的脾细胞的流式细胞仪分析表明，皮内免疫导致最大的群体的生发中心和活化的B细胞转化为更高的抗体水平和抗原特异性CTL应答。我们的研究结果表明，VLP交通进入淋巴结免疫后，可以直接可视化的光学成像技术。皮内免疫显示出改善的反应，可能是一个更好的交付途径，用于病毒和癌症免疫研究涉及VLP。
Virus-like particles (VLPs) have gained increasing interest for their use as vaccines due to their repetitive antigenic structure which is capable of efficiently activating the immune system. The efficacy of virus-like particle immunization may lie in its ability to traffic into draining lymph nodes while activating antigen-presenting cells in order to initiate the orchestration of signals required for the development of a robust immune response. Currently, there is no comprehensive study showing the correlation of different VLP vaccination routes to immune outcome. In this study, we took an optical imaging approach to directly visualize the trafficking of SHIV VLPs after immunization by commonly used routes and analyzed the corresponding humoral and cellular immune responses generated. We found that VLPs can easily enter the subcapsular sinus of draining lymph nodes with quantitative differences in the number of lymph node involvement depending on the immunization route used. Intradermal immunization led to the largest level of lymph node involvement for the longest period of time, which correlated with the strongest humoral and cellular immune responses. Flow cytometry analysis from extracted splenocytes showed that intradermal immunization led to the largest population of germinal center and activated B cells which translated into higher antibody levels and antigen-specific CTL responses. Our results indicate that VLPs traffic into lymph nodes upon immunization and can be directly visualized by optical imaging techniques. Intradermal immunization showed improved responses and might be a preferable delivery route to use for viral and cancer immunotherapeutic studies involving VLPs.