Development of novel vaccine system with nanocarrier

我们发现，第二剂量的PEG化脂质体被积极地从边缘区（MZ）运输到脾脏中的卵泡，当它们以短间隔注射到同一只大鼠中时1。我们发现，脾MZ B细胞捕获并运输第二剂量脂质体进入卵泡后的时间依赖性方式。捕获并转运的脂质体最终被滤泡树突状细胞摄取。我们试图将这种独特的免疫应答应用于一种新的佐剂系统，该系统增强了针对包封在第二剂量脂质体中的抗原的特异性抗体应答。用低剂量空脂质体预免疫，其触发含抗原的第二剂量脂质体转运到卵泡中，诱导抗-OVA IgM和抗-OVA IgG产生，因为含OVA的脂质体而不是游离OVA作为第二剂量静脉内注射。制备的抗OVA IgG含有IgG 1、IgG 2a和IgG 2b亚类。此外，免疫后高水平的抗-OVA IgG持续超过12周。这些表明用空PEG化脂质体预刺激可增强针对包封在第二剂量脂质体中的抗原的特异性抗体应答。我们的结论是，我们的主动运输方法可以是有用的一种新的和替代的疫苗策略，以加强特异性抗体反应。

We showed that second dose PEGylated liposome is aggressively transported from marginal zone (MZ) into follicle in spleen when they are injected twice into the same rat with short interval1. We revealed that splenic MZ B cells capture and transport second dose liposomes into follicle in a time after second dose injection-dependent manner. The captured and then transported liposomes were finally taken up by follicular dendritic cell. We tried to apply this unique immune response to be a novel adjuvant system which enhances a specific antibody response against antigen encapsulated in second dose liposomes. Pre-immunization with low dose empty liposome, which triggers the transport of antigen-containing second dose liposomes into follicle, induced both anti-OVA IgM and anti-OVA IgG productions as OVA-containing liposomes, not free OVA, was intravenously injected as a second dose. The produced anti-OVA IgG contained IgG1, IgG2a and IgG2b subclasses. In addition, the high level of anti-OVA IgG lasted over 12 weeks after the immunization. These suggest that pre-stimulation with empty PEGylated liposomes could enhance the specific antibody response against antigen encapsulated in second dose liposomes. We conclude that our active transport methodology can be useful for a novel and alternative vaccine strategy to potentiate specific antibody response.