Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs.
Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs.
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DOI：
10.1016/j.virusres.2016.10.007
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发表时间：
2017-01-02
期刊：
影响因子：
5
通讯作者：
Meng XJ
中科院分区：
文献类型：
--
作者：
Subramaniam S;Cao D;Tian D;Cao QM;Overend C;Yugo DM;Matzinger SR;Rogers AJ;Heffron CL;Catanzaro N;Kenney SP;Opriessnig T;Huang YW;Labarque G;Wu SQ;Meng XJ
通过单链抗体将PEDV刺突蛋白结构域靶向表达Langerin的树突状细胞。经皮靶向PEDV S抗原的朗格林显著增强CD_4- T细胞免疫功能。系统靶向PEDV S抗原可显著增强血清Ig G和Ig A应答。猪流行性腹泻病毒(PEDV)于2013年首次出现在美国，造成新生仔猪高死亡率和高发病率，给养猪业造成了巨大的经济损失。PEDV是一种主要在猪肠道细胞中复制的甲型冠状病毒。PEDV疫苗在亚洲和欧洲都可以买到，美国最近也有了有条件许可的疫苗，但这些疫苗在从猪群中消除PEDV方面的效果值得怀疑。本研究以猪树突状细胞(DC)为靶点，研究了基于PEDV S蛋白的亚单位疫苗的免疫原性。用针对朗格林的单链抗体将S抗原导入树突状细胞，用霍乱毒素佐剂刺激靶细胞。这种被称为“树突状细胞靶向”的方法，在猪经皮给药后7天，就极大地改善了猪CD4posCD8pos T细胞室中PEDV S抗原特异性T细胞干扰素-γ的反应。当疫苗蛋白通过肌肉注射系统地靶向Langerinpos DC时，它在猪体内诱导了更高的血清IgG和IgA应答，尽管这些应答需要加强剂量，而且与经皮免疫相比，T细胞应答的幅度更低。我们的结论是，针对表达朗格林的树突状细胞的PEDV尖峰蛋白结构域显著增加了猪的CD4CD4T细胞免疫应答。结果表明，将疫苗抗原直接靶向猪树突状细胞亚群，可大大提高蛋白质亚单位疫苗的免疫原性。
Targeting PEDV spike protein domains to Langerin-expressing dendritic cells through a single chain antibody. Transdermal Langerin-targeting of PEDV S antigen significantly enhanced CD4 T cell immunity. Systemic Langerin-targeting of PEDV S antigen significantly augmented serum IgG and IgA responses. Porcine epidemic diarrhea virus (PEDV) first emerged in the United States in 2013 causing high mortality and morbidity in neonatal piglets with immense economic losses to the swine industry. PEDV is an alpha-coronavirus replicating primarily in porcine intestinal cells. PEDV vaccines are available in Asia and Europe, and conditionally-licensed vaccines recently became available in the United States but the efficacies of these vaccines in eliminating PEDV from swine populations are questionable. In this study, the immunogenicity of a subunit vaccine based on the spike protein of PEDV, which was directly targeted to porcine dendritic cells (DCs) expressing Langerin, was assessed. The PEDV S antigen was delivered to the dendritic cells through a single-chain antibody specific to Langerin and the targeted cells were stimulated with cholera toxin adjuvant. This approach, known as “dendritic cell targeting,” greatly improved PEDV S antigen-specific T cell interferon-γ responses in the CD4posCD8pos T cell compartment in pigs as early as 7 days upon transdermal administration. When the vaccine protein was targeted to Langerinpos DCs systemically through intramuscular vaccination, it induced higher serum IgG and IgA responses in pigs, though these responses require a booster dose, and the magnitude of T cell responses were lower as compared to transdermal vaccination. We conclude that PEDV spike protein domains targeting Langerin-expressing dendritic cells significantly increased CD4 T cell immune responses in pigs. The results indicate that the immunogenicity of protein subunit vaccines can be greatly enhanced by direct targeting of the vaccine antigens to desirable dendritic cell subsets in pigs.
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