Polarizing T and B Cell Responses by APC-Targeted Subunit Vaccines.
Polarizing T and B Cell Responses by APC-Targeted Subunit Vaccines.
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DOI：
10.3389/fimmu.2015.00367
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发表时间：
2015
影响因子：
7.3
通讯作者：
Bogen B
中科院分区：
文献类型：
--
作者：
Grødeland G;Fossum E;Bogen B
目前的流感疫苗大多旨在诱导特定的中和抗体。虽然抗体对于抵御特定病毒株很重要，但T细胞可以识别将提供更广泛保护以抵御流感的表位。我们之前已经开发出一种DNA疫苗形式，通过这种形式，蛋白质抗原可以特异性地靶向抗原提呈细胞(APC)上的受体。DNA编码的疫苗蛋白是同源二聚体，每个链由一个靶向单元、一个二聚化单元和一个抗原组成。与非靶向对照相比，靶向APC的策略大大增强了免疫反应。此外，将抗原靶向于APC上的不同受体可以使不同免疫臂的免疫反应两极分化。在这里，我们讨论了血凝素靶向MHC II类分子如何增加Th2和IgG1抗体应答，而靶向趋化因子受体XCR1或CCR1/3/5除了CD8+T细胞应答外还增加Th1和IgG2a应答。我们还讨论了与其他人发表的关于APC目标的工作有关的这些结果。APC表面分子的不同靶向可能允许诱导量身定制的适应性免疫反应的表型，这些表型对于保护包括流感病毒在内的各种感染源是最佳的。
Current influenza vaccines mostly aim at the induction of specific neutralizing antibodies. While antibodies are important for protection against a particular virus strain, T cells can recognize epitopes that will offer broader protection against influenza. We have previously developed a DNA vaccine format by which protein antigens can be targeted specifically to receptors on antigen presenting cells (APCs). The DNA-encoded vaccine proteins are homodimers, each chain consisting of a targeting unit, a dimerization unit, and an antigen. The strategy of targeting antigen to APCs greatly enhances immune responses as compared to non-targeted controls. Furthermore, targeting of antigen to different receptors on APCs can polarize the immune response to different arms of immunity. Here, we discuss how targeting of hemagglutinin to MHC class II molecules increases Th2 and IgG1 antibody responses, whereas targeting to chemokine receptors XCR1 or CCR1/3/5 increases Th1 and IgG2a responses, in addition to CD8+ T cell responses. We also discuss these results in relation to work published by others on APC-targeting. Differential targeting of APC surface molecules may allow the induction of tailor-made phenotypes of adaptive immune responses that are optimal for protection against various infectious agents, including influenza virus.