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H9N2流感全灭活病毒与聚乙烯亚胺联合使用,在小鼠鼻内免疫后能显著增强黏膜免疫和全身免疫。

H9N2 influenza whole inactivated virus combined with polyethyleneimine strongly enhances mucosal and systemic immunity after intranasal immunization in mice.

作者信息

Qin Tao, Yin Yinyan, Huang Lulu, Yu Qinghua, Yang Qian

机构信息

Key Lab of Animal Physiology and Biochemistry of China's Department of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People's Republic of China.

Key Lab of Animal Physiology and Biochemistry of China's Department of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People's Republic of China

出版信息

Clin Vaccine Immunol. 2015 Apr;22(4):421-9. doi: 10.1128/CVI.00778-14. Epub 2015 Feb 11.

Abstract

Influenza whole inactivated virus (WIV) is more immunogenic and induces protective antibody responses compared with other formulations, like split virus or subunit vaccines, after intranasal mucosal delivery. Polyethyleneimine (PEI), an organic polycation, is widely used as a reagent for gene transfection and DNA vaccine delivery. Although PEI recently has demonstrated potent mucosal adjuvant activity for viral subunit glycoprotein antigens, its immune activity with H9N2 WIV is not well demonstrated. Here, mice were immunized intranasally with H9N2 WIV combined with PEI, and the levels of local respiratory tract and systemic immune responses were measured. Compared to H9N2 WIV alone, antigen-specific IgA levels in the local nasal cavity, trachea, and lung, as well as levels of IgG and its subtypes (IgG1 and IgG2a) in the serum, were strongly enhanced with the combination. Similarly, the activation and proliferation of splenocytes were markedly increased. In addition, PEI is superior as an H9N2 WIV delivery system due to its ability to greatly increase the viral adhesion to mucosal epithelial cells and to enhance the cellular uptake and endosomal escape of antigens in dendritic cells (DCs) and further significantly activate DCs to mature. Taken together, these results provided more insights that PEI has potential as an adjuvant for H9N2 particle antigen intranasal vaccination.

摘要

与其他剂型(如裂解病毒疫苗或亚单位疫苗)相比,流感全病毒灭活疫苗(WIV)经鼻内黏膜接种后具有更强的免疫原性,并能诱导产生保护性抗体反应。聚乙烯亚胺(PEI)是一种有机聚阳离子,广泛用作基因转染试剂和DNA疫苗递送剂。尽管PEI最近已证明对病毒亚单位糖蛋白抗原有强大的黏膜佐剂活性,但其与H9N2 WIV的免疫活性尚未得到充分证明。在此,用H9N2 WIV联合PEI对小鼠进行鼻内免疫,并检测局部呼吸道和全身免疫反应水平。与单独使用H9N2 WIV相比,联合使用时局部鼻腔、气管和肺部的抗原特异性IgA水平以及血清中IgG及其亚型(IgG1和IgG2a)的水平均显著提高。同样,脾细胞的活化和增殖也明显增加。此外,PEI作为H9N2 WIV的递送系统具有优势,因为它能够大大增加病毒与黏膜上皮细胞的粘附,并增强树突状细胞(DCs)对抗原的细胞摄取和内体逃逸,进而显著激活DCs成熟。综上所述,这些结果为PEI作为H9N2颗粒抗原鼻内疫苗的佐剂具有潜力提供了更多见解。

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