Pulmonary delivery of DNA vaccine constructs using deacylated PEI elicits immune responses and protects against viral challenge infection.
Pulmonary delivery of DNA vaccine constructs using deacylated PEI elicits immune responses and protects against viral challenge infection.
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DOI：
10.1016/j.jconrel.2013.06.004
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发表时间：
2013-09-28
期刊：
影响因子：
--
通讯作者：
Shattock RJ
中科院分区：
文献类型：
--
作者：
Mann JF;McKay PF;Arokiasamy S;Patel RK;Klein K;Shattock RJ
通过粘膜表面接种疫苗已被证明能激发针对许多粘膜病原体的抗病毒免疫反应。在这里，我们证明了当阳离子复杂的质粒DNA疫苗局部应用于小鼠肺粘膜作为免疫启动策略时，针对模型HIV-1CN54gp140抗原的粘膜和系统免疫反应都可以被激发。此外，使用流感挑战模型，我们表明，与称为dPEI的毒性较低的PEI(一种几乎完全水解线性PEI，附加11%的游离可质子化氮原子)复合的质粒DNA疫苗可以显著保护小鼠免受呼吸道挑战性感染。此外，我们还发现dPEI复合体不仅有可能进入粘膜上皮细胞，还可以通过调节紧密连接的完整性深入到组织中。综上所述，这些结果表明，毒性较低的PEI形式可以有效地运送质粒DNA，在体内引发细胞和体液保护反应。此外，我们的观察表明，这些毒性较低的PEI衍生物可用于将局部质粒DNA疫苗输送到人的粘膜组织表面，这种应用可能允许免疫反应通过连接的粘膜网络传播，从而在病原体进入的远端门户提供保护性免疫。
Vaccination through mucosal surfaces has been shown to elicit antiviral immune responses against a number of mucosal pathogens. Here we demonstrate that both mucosal and systemic immune responses can be elicited against a model HIV-1 CN54gp140 antigen when cation-complexed plasmid DNA vaccines are applied topically to the murine pulmonary mucosa as an immune priming strategy. Furthermore, using an influenza challenge model we show that a plasmid DNA vaccine complexed to a less toxic form of PEI called dPEI (a nearly fully hydrolysed linear PEI with 11% additional free protonatable nitrogen atoms) can provide significant protection against a respiratory challenge infection in mice. Furthermore, we show that dPEI polyplexes have the potential to transfect not only mucosal epithelium, but also to enter deeper into tissues through the modulation of tight junction integrity. Taken together, these results demonstrate that less toxic forms of PEI can be effective delivery vehicles for plasmid DNAs to elicit cellular and humoral protective responses in vivo. Moreover, our observations suggest that these less toxic derivatives of PEI could be utilised for topical plasmid DNA vaccine delivery to human mucosal tissue surfaces, and that this application may permit dissemination of the immune responses through the linked mucosal network thus providing protective immunity at distal portals of pathogen entry.
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DOI：
10.1084/jem.184.5.1879
发表时间：
1996-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gallichan WS;Rosenthal KL
通讯作者：
Rosenthal KL
DOI：
10.1016/j.jconrel.2011.11.009
发表时间：
2012-03-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Mann JF;Stieh D;Klein K;de Stegmann DS;Cranage MP;Shattock RJ;McKay PF
通讯作者：
McKay PF
影响因子：
3.7
作者：
Thomas, Mini;Lu, James J.;Klibanov, Alexander M.
通讯作者：
Klibanov, Alexander M.
影响因子：
4.3
作者：
Hunter, A. Christy;Moghimi, S. Moein
通讯作者：
Moghimi, S. Moein
影响因子：
6.7
作者：
Im EJ;Hong JP;Roshorm Y;Bridgeman A;Létourneau S;Liljeström P;Potash MJ;Volsky DJ;McMichael AJ;Hanke T
通讯作者：
Hanke T