中文摘要：研究了利用鞭毛蛋白融合HA1-2提高鸡对H7N9流感病毒的体液和细胞免疫反应的可行性。研究分析了鞭毛蛋白体外和体内诱导的不同禽类免疫细胞中细胞因子和化学增活素的表达量。结果表明：鞭毛蛋白显著提高了禽类巨噬细胞HD11中CXCL炎性化学增活素和CCL化学增活素的表达水平。利用HA1-2-fliC能够显著提高血浆中HA1-2特异性免疫球蛋白IgG的滴度。HA1-2-fliC能够提高CD4(+) 和 CD8(+) T的浓度，促进PBMCs增殖；同时能够促进Th1/Th2免疫反应的平衡。该研究结果表明，鞭毛蛋白是HA1-2亚单位疫苗的理想佐剂，可用于制备鸡抗H7N9流感HA1-2亚单位疫苗的制备。
外文摘要：Background: Sudden increases in the number of human A (H7N9) cases reported during December and January have been observed in previous years. Most reported infection cases are due to prior exposure to live poultry or potentially contaminated environments. Low pathogenicity of influenza A (H7N9) virus in avian species complicates timely discovery of infected birds. Therefore, there is a pressing need to develop safe and effective anti-H7N9 vaccines for poultry to reduce the risk of human infection and prevent the emergence of novel mutated strains. In addition to a good antigen, an effective vaccine also requires an appropriate adjuvant to enhance its immunogenicity. Previously, we generated an H7N9 influenza recombinant subunit vaccine (HA1-2-fliC), in which haemagglutinin globular head domain (HA1-2) was fused with flagellin (fliC), a potent TLR5 ligand, and demonstrated that HA1-2-fliC elicited effective HA1-2-specific immune responses in mice. Results: In this study, we determined flagellin-induced expression profiles of cytokines and chemokines in different types of avian immune cells in vitro and ex vivo. We found that flagellin significantly increased the expression levels of CXCL inflammatory chemokines (CXCLi1 and CXCLi2) and CCL chemokines (MIP-1 beta and MCP-3) in avian macrophage HD11 cells. In addition, HA1-2-fliC induced significant upregulation of cytokines (IL-1 beta, IL-6, IL-18 and IFN-gamma) and chemokines (CXCLi1, CXCLi2 and MIP-1 beta) in ex vivo splenic lymphocytes and peripheral blood mononuclear cells (PBMCs), suggesting that flagellin promoted immune responses of avian cells in vitro. We also evaluated specific humoural and cellular immune responses induced by HA1-2-fliC and found that chickens immunised intramuscularly with HA1-2-fliC showed significantly higher HA1-2-specific immunoglobulin (Ig)G titers in serum. Furthermore, HA1-2-fliC potentiated cellular immune responses, as reflected by an increase in CD4(+) and CD8(+) T cells and proliferation of PBMCs. Significantly higher levels of IFN-gamma and IL-4 in PBMCs from chickens vaccinated with HA1-2-fliC further indicated that HA1-2fliC promoted a balanced Th1/Th2 immune response. Conclusions: We demonstrated that the use of the flagellin as an adjuvant potentiated immunogenicity of influenza subunit vaccine HA1-2 in vitro and in vivo. These findings provide a basis for the development of H7N9 influenza HA1-2 subunit vaccines for chickens.
外文关键词：Avian influenza A (H7N9) virus； Haemagglutinin globular head； Flagellin； Subunit vaccine； Chicken
作者： Song, L; Xiong, D; Hu, MZ; Kang, XL; Pan, ZM; Jiao, XN
作者单位：扬州大学
期刊名称：BMC VETERINARY RESEARCH
期刊影响因子：1.83
出版年份：2017
出版刊次：6
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