The Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Nat Biotechnol. 2012 Sep;30(9):883-8. doi: 10.1038/nbt.2344.
Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry, yet there are no mucosal adjuvant formulations licensed for human use. Polyethyleneimine (PEI) represents a family of organic polycations used as nucleic acid transfection reagents in vitro and DNA vaccine delivery vehicles in vivo. Here we show that diverse PEI forms have potent mucosal adjuvant activity for viral subunit glycoprotein antigens. A single intranasal administration of influenza hemagglutinin or herpes simplex virus type-2 (HSV-2) glycoprotein D with PEI elicited robust antibody-mediated protection from an otherwise lethal infection, and was superior to existing experimental mucosal adjuvants. PEI formed nanoscale complexes with antigen, which were taken up by antigen-presenting cells in vitro and in vivo, promoted dendritic cell trafficking to draining lymph nodes and induced non-proinflammatory cytokine responses. PEI adjuvanticity required release of host double-stranded DNA that triggered Irf3-dependent signaling. PEI therefore merits further investigation as a mucosal adjuvant for human use.
针对黏膜传播感染的保护可能需要病原体进入部位的免疫，但目前尚无获准用于人体的黏膜佐剂制剂。聚乙烯亚胺（PEI）是一类有机多阳离子，用作体外核酸转染试剂和体内 DNA 疫苗传递载体。在这里，我们表明，多种 PEI 形式对病毒亚单位糖蛋白抗原具有有效的黏膜佐剂活性。流感血凝素或单纯疱疹病毒 2 型（HSV-2）糖蛋白 D 与 PEI 单次鼻腔给药可引发针对致命感染的强大抗体介导的保护作用，优于现有的实验性黏膜佐剂。PEI 与抗原形成纳米级复合物，这些复合物在体外和体内被抗原呈递细胞摄取，促进树突状细胞向引流淋巴结迁移，并诱导非炎症性细胞因子反应。PEI 的佐剂活性需要释放宿主双链 DNA，从而触发 Irf3 依赖性信号转导。因此，PEI 值得进一步研究作为人类使用的黏膜佐剂。
