Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Vaccine. 2011 Jan 29;29(5):1045-52. doi: 10.1016/j.vaccine.2010.11.061. Epub 2010 Dec 1.
Enhanced immunogenicity of subunit antigens can be achieved by antigen encapsulation in liposomes and the addition of immune potentiators. In this study we co-encapsulated ovalbumin (OVA) and a Toll-like receptor (TLR) ligand (PAM(3)CSK(4) (PAM) or CpG) in cationic liposomes and investigated the effect of the formulations on dendritic cell (DC) maturation in vitro and on the immune response in mice after intradermal immunisation. Co-encapsulation of PAM did not affect the OVA content of the liposomes, but co-encapsulation of CpG led to a decrease in OVA content by 25%. After liposomal encapsulation, both ligands retained the ability to activate TLR-transfected HEK cells, though PAM only induced activation at elevated concentrations. DC maturation induced by liposome-based adjuvant formulations was superior compared to the free adjuvants. Encapsulation of PAM and CpG in liposomes did not influence the total IgG titres compared to the antigen/adjuvant solution, but OVA/CpG liposomes shifted the IgG1/IgG2a balance more to the direction of IgG2a compared to non-encapsulated CpG. Moreover, only this formulation resulted in IFN-γ production by restimulated splenocytes from immunised mice. These data show that co-encapsulation of antigen and immune potentiator in cationic liposomes, can affect the type of immune response generated after intradermal immunisation.
通过将抗原包裹在脂质体中并添加免疫增强剂，可以增强亚单位抗原的免疫原性。在这项研究中，我们将卵清蛋白（OVA）和 Toll 样受体（TLR）配体（PAM（3）CSK（4）（PAM）或 CpG）共同包裹在阳离子脂质体中，并研究了这些配方对体外树突状细胞（DC）成熟和经皮免疫后小鼠免疫反应的影响。PAM 的共包封不会影响脂质体中的 OVA 含量，但 CpG 的共包封会导致 OVA 含量减少 25%。脂质体包封后，两种配体都保留了激活 TLR 转染的 HEK 细胞的能力，尽管 PAM 仅在高浓度下诱导激活。与游离佐剂相比，基于脂质体的佐剂配方诱导的 DC 成熟更为优越。与抗原/佐剂溶液相比，PAM 和 CpG 的包封对总 IgG 滴度没有影响，但 OVA/CpG 脂质体与未包封的 CpG 相比，将 IgG1/IgG2a 平衡更偏向 IgG2a。此外，只有这种配方可导致免疫小鼠的脾细胞经再刺激后产生 IFN-γ。这些数据表明，将抗原和免疫增强剂共同包裹在阳离子脂质体中，可以影响经皮免疫后产生的免疫反应类型。
