Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses.

Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses.
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DOI:
10.1186/1471-2172-11-65
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发表时间:
2010-12-31
期刊:
影响因子:
3
通讯作者:
Yun CH
Yun CH
中科院分区:
医学4区
文献类型:
--
作者:
Shim BS;Park SM;Quan JS;Jere D;Chu H;Song MK;Kim DW;Jang YS;Yang MS;Han SH;Park YH;Cho CS;Yun CH

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用严重急性呼吸综合征(SARS)冠状病毒(CoV)的刺突蛋白(S)免疫小鼠,已知可产生中和抗体并预防SARS-CoV引起的感染。聚乙烯亚胺25K(PEI)是一种阳离子聚合物,可有效递送质粒DNA。在本研究中,通过鼻内(i.n.)研究了PEI/pci-S复合物形式的SARS DNA疫苗(pci-S)的免疫途径。PEI/pci-S纳米颗粒的大小约为194.7 ± 99.3 nm,并在体外证实了S mRNA和蛋白的表达。用i.n. PEI/pci-S纳米粒在血清中产生的S特异性IgG1和在肺洗液中产生的粘膜分泌型IgA显著高于单独用pci-S处理的小鼠(P <0.05)。与单独用pci-S攻击的小鼠相比,在PEI/pci-S接种的小鼠中发现的B220+细胞的数量增加。PEI/pci-S疫苗接种后,小鼠颈淋巴结中CD11c+树突状细胞表面共刺激分子(CD80和CD86)和II类主要组织相容性复合物分子(I-Ad)表达增加。PEI/pci-S免疫小鼠产生IFN-γ、TNF-α和IL-2的细胞百分比高于对照小鼠。这些结果表明,用PEI/pci-S纳米颗粒鼻内免疫诱导抗原特异性体液和细胞免疫应答。
Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA. In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220+ cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-Ad) were increased on CD11c+ dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.
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