Development of novel vaccine adjuvant for infectious disease

将常规脂质体与紫外线灭活仙台病毒融合制备促聚变脂质体。融合性脂质体可以以仙台病毒融合依赖的方式直接将包裹的内容物递送到细胞质中。基于高递送率进入细胞质，我们研究了使用融合性脂质体作为抗原递送载体。采用融合性脂质体对抗原进行鼻腔给药，有效地将抗原递送到鼻咽部相关淋巴网状组织的抗原取样M细胞中。此外，融合性脂质体还能有效地将抗原递送到鼻咽相关淋巴网状组织和鼻道的上皮细胞和巨噬细胞中。体外抗原呈递实验清楚地表明，融合性脂质体通过上皮细胞和巨噬细胞的MHC ii类依赖途径有效地呈递包裹抗原。融合性脂质体也对粘膜上皮细胞具有佐剂活性，可增强MHC II类表达。根据这些高递送和佐剂活性，用ova包膜的fusogenic lipo质体鼻腔免疫可诱导高水平的ova特异性CD4(+) Th1和Th2细胞应答。此外，抗原特异性CTL反应和抗体的产生也可以通过抗原包裹的融合性脂质体鼻腔免疫在粘膜和全身部位引起。这些结果表明，融合性脂质体是一个多功能和有效的系统刺激抗原特异性免疫反应在粘膜和系统室。

We prepared fusogenic liposomes by fusing conventional liposomes with an ultra-violet inactivated Sendai virus. Fusogenic liposomes can deliver encapsulated contents into the cytoplasm directly in a Sendai virus fusion-dependent manner. Based on the high delivery rates into the cytoplasm, we examined the use of fusogenic liposomes as an antigen delivery vehicle. Nasal administration of antigens using fusogenic liposome efficiently delivered antigens to antigen-sampling M cells in nasopharyngeal-associated lymphoreticular tissue. Additionally, fusogenic liposomes also effectively delivered the antigens into epithelial cells and macrophages in nasopharyngeal-associated lymphoreticular tissue and nasal passages. In vitro Antigen presentation assays clearly showed that fusogenic liposomes effectively presented encapsulated antigens via the MHC class II-dependent pathway of epithelial cells as well as macrophages. Fusogenic liposomes also have an adjuvant activity against mucosal epithelial cells to enhance MHC class II expression. According to these high delivery and adjuvant activities of fusogenic liposomes, nasal immunization with OVA-encapsulated fusogenic liposomes induced high levels of OVA-specific CD4(+) Th1 and Th2 cell responses. Furthermore, Antigen-specific CTL responses and antibody productions were also elicited at both mucosal and systemic sites by nasal immunization with antigen-encapsulated fusogenic liposomes. These results indicate that fusogenic liposome is a versatile and effective system for the stimulation of antigen-specific immune responses at both mucosal and systemic compartments.