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以聚乳酸-羟基乙酸共聚物(PLGA)为疫苗递送和佐剂系统,采用快速膜乳化技术制备了粒径0.43和1.38μm的均一PLGA微球,以其包埋HPV L1五聚体抗原,考察微球粒径对体内免疫应答强度和水平的影响.结果表明,1.38μm粒径载抗原PLGA微球组产生的IgG滴度(87771±24983.0)和中和抗体滴度(30720±15863.7)显著高于0.43μm粒径组的IgG滴度(38400±14021.7)(P<0.05)和中和抗体滴度(2480±3892.6)(P<0.01),且1.38μm载抗原PLGA微球能更显著提高Th2型细胞因子IL-6(0.43μm微球的4.7倍)和IL-4(0.43μm微球的1.5倍)的分泌水平;而0.43μm载抗原PLGA微球能显著提升Th1型细胞因子IFN-γ(1.38μm微球的2.1倍)的分泌水平,表明对于HPV疫苗佐剂与递送系统,小粒径微球有利于细胞免疫的提升,可用于治疗性疫苗的开发;而大粒径微球则有利于诱导高效体液免疫,可用于预防性疫苗的开发.
Polylactic-co-glycolic acid (PLGA) was used as vaccine delivery and adjuvant system, and uniform PLGA microspheres with particle size of 0.43 and 1.38 μm were prepared by rapid membrane emulsification. The results showed that IgG titer (87771 ± 24983.0) and neutralizing antibody titers (30720 ± 15863.7) produced by PLGA microspheres with 1.38μm particle size were significantly higher than those of PLGA microspheres The IgG titer (38400 ± 14021.7) and neutralizing antibody titers (2480 ± 3892.6) in the 0.43μm particle group (P <0.01), and the PLGA microspheres with 1.38μm carrier antigen could significantly increase the Th2 The secretion of cytokines IL-6 (4.7-fold with 0.43μm microspheres) and IL-4 (1.5-fold with 0.43μm microspheres), while the PLGA microspheres with 0.43μm carrier antigen could significantly enhance the secretion of Th1-type cytokines IFN- 2.1-fold higher than 1.38μm microspheres), indicating that small particle size microspheres are good for cellular immune enhancement for HPV vaccine adjuvants and delivery systems and are useful for the development of therapeutic vaccines, whereas larger particle size microspheres have Conducive to inducing efficient humoral immunity, can be used for the development of preventive vaccines.