靶向CD205+和XCR1+DC亚群的乙肝治疗性疫苗构建及其效应研究

Chronic HBV carrier is deficient at initiating cell-mediated immunity and fails to eliminate the intracellular virus. In the project, we aimed to break the immune tolerance via enhancing efficiency of HBV antigen delivery and cross-presentation. The cross-presentation of antigen is presently considered closely related with CD205+ DC and XCR1+ DC subset. The delivery of HBV antigen could be targeted DC subset via CD205 antibody and XCR1 ligand XCL1, which might enhance the efficiency of HBV antigens phagocytosis, and promote cross-presentation. The efficiently delivery of HBV antigen could also be achieved by nanometer particle. There exists the pattern recognition receptors on the DCs, which could be activated by targeting the intracellular receptor ligand PolyIC, R848 or CpG to DC subset. The targeting nanometer particles containing the above PRR ligand could achieve targeted delivery and activation of DC subset. These particle-based novel strategies could increase antigen uptake by DCs, improve the cross-presentation, and provide the full potential for inducing effective cellular immune response.

HBV慢性感染患者很难诱导有效的细胞免疫，无法清除胞内感染的乙肝病毒。本课题拟通过增强HBV抗原的高效递送和交叉提呈，打破HBV的免疫耐受。目前认为同抗原的交叉提呈密切相关DC亚群包括CD205+DC和XCR1+DCs，将HBV抗原与CD205抗体和XCR1天然配体XCL1的联合使用，实现抗原的靶向递送，增加HBV抗原的吞噬效率，促进交叉提呈。通过构建基于PLGA的纳米颗粒实现抗原的高效递送。基于DCs上的模式识别受体，构建基于PRR的配体PolyIC、R848或CpG等胞内受体纳米颗粒，实现靶向递送，活化DC功能，辅助HBV抗原的交叉提呈。通过以上构建高效的靶向纳米系统，希望以此增加抗原的递送效率、促进抗原的交叉提呈、提高细胞免疫应答。