J Immunol：新型疫苗有望预防流感病毒
利用树突状细胞识别特定抗原物质能够增强抗原特异性免疫反应。尽管树突状细胞靶向抗原的主要作用是增强T细胞反应，但许多研究也表明这一策略能够有效提高抗体的产生水平。事实上，不仅特异性与MHC-II分子识别的抗原物质，而且与CD11C，CD180等表面受体结合的分子也能够显著增强抗体的反应。然而，抗体产生的多少取决于受到激活的受体种类。早期的研究通过将抗体与特定的靶向抗原物质交联，用于刺激树突状细胞表面的分子标记。其中包括MHC-II，CCR-5，CD40、CD14以及Xcr1等等。试验结果表明这些疫苗分子均能够增强癌症或感染中的免疫反应。特别地，靶向Xcr1分子的融合疫苗在诱导小鼠抗流感免疫反应中有着明显的效果。
最近，来自挪威的研究者们根据人源的XCL1与XCL2设计了融合疫苗，该疫苗均能够靶向人体抗原呈递细胞中的XCR1受体。然后利用上述两种疫苗进行了小鼠水平的抗流感免疫反应的诱导。相关结果发表在最近一期的《Journal of Immunology》杂志上。
首先，作者对上述两类融合疫苗进行了特征分析。结果显示，这两类疫苗能够与小鼠来源的CXR1阳性的树突状细胞相互结合并发生反应。之后，他们发现这两类疫苗与流感病毒抗原HA共同接种能够保护小鼠免受致死剂量的流感病毒的感染。进一步，他们发现在进行了上述接种之后，小鼠体内出现了快速的体液与细胞免疫。与传统的NIP-HA疫苗相比，这种疫苗能够显著提高抗体的产生水平。
综上，作者通过一系列试验表明靶向人源的Xcr1设计的融合疫苗同样具有潜在的预防流感的效果。
来源：生物谷
Targeting Influenza Virus Hemagglutinin to Xcr1+ Dendritic Cells in the Absence of Receptor-Mediated Endocytosis Enhances Protective Antibody Responses
Arnar Gudjonsson, Anna Lysén, Sreekumar Balan, Vibeke Sundvold-Gjerstad, Catharina Arnold-Schrauf, Lisa Richter, Espen S. Bækkevold, Marc Dalod, Bjarne Bogen and Even Fossum
Targeting Ags to conventional dendritic cells can enhance Ag-specific immune responses. Although most studies have focused on the induction of T cell responses, the mechanisms by which targeting improves Ab responses are poorly understood. In this study we present data on the use of human XCL1 (hXCL1) and hXCL2 fusion vaccines in a murine model. We show that the human chemokines bound type 1 conventional dendritic cells (cDC1), and that immunization with influenza virus hemagglutinin fused to hXCL1 or hXCL2 induced full protection against influenza challenge. Surprisingly, the hXCL1- and hXCL2-fusion vaccines induced better long-term protection associated with stronger induction of neutralizing Abs, and more Ab-secreting cells in bone marrow. In contrast, murine Xcl1 fusion vaccines induced stronger CD8+ T cell responses compared with hXCL1. Further analysis revealed that although murine Xcl1 fusion vaccines induced chemotaxis and were rapidly endocytosed by cDC1, hXCL1 and hXCL2 fusion vaccines did not induce chemotaxis, were less efficiently endocytosed, and consequently, remained on the surface. This difference may explain the enhanced induction of Abs when targeting Ag to cDC1 using hXCL1 and hXCL2, and suggests that immune responses can be manipulated in directing Abs or T cells based on how efficiently the targeted Ag is endocytosed by the DC.
http://www.jimmunol.org/content/early/2017/02/21/jimmunol.1601881?papetoc
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