PLGA微球粒径对HPV L1五聚体候选疫苗免疫效果的调控  

Effect of PLGA Microsphere Size on Regulation of Immune Response for HPV L1 Capsomere-based Candidate Vaccine

作　　者：贾成成[1,2] 王连艳[2] 方颖[1] 陈健平[3] 曹科 刘永江 马光辉[2] 

机构地区：[1]华南理工大学生物科学与工程学院,广东广州510006 [2]中国科学院过程工程研究所生化工程国家重点实验室,北京100190 [3]北京康乐卫士生物技术有限公司,北京100176

出　　处：《过程工程学报》2013年第4期638-645,共8页The Chinese Journal of Process Engineering

摘　　要：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.Two-sized poly（lactic-co-glycolic acid） （PLGA） microspheres prepared by membrane emulsification technique were used as vaccine delivery and adjuvant system. The effect of particle size on enhancing HPV L1 specific immune responses was investigated. The results showed that HPV L1 pentamers encapsulated in large-sized PLGA （1.38 ~tm） microspheres could elicit significantly higher level of IgG binding antibodies （87771＋_24983.0） and neutralizing antibodies （30720＋15863.7） than the counterparts with 0.43 ~tm （38400＋14021.7） and （2480＋3 892.6） （P〈0.05 and P〈0.01）. The similar trend was also found in cytokine secretion levels, and higher levels oflL-6 （4.7 times of the cytokines for small-sized microspheres） and IL-4 （1.5 times of the cytokines for small-sized microspheres） were observed in mice immunized with large-sized PLGA microspheres （1.38 lam） encapsulating HPV L1 pentamers. While small-sized PLGA microspheres （0.43 Ixm） encapsulating HPV L1 pentamers elicited significantly higher IFN-7 secretion levels （2.1 times of the cytokine for the large-sized microspheres） than large-sized PLGA microspheres （1.38 ixm）. Small-sized PLGA microspheres can enhance antigen specific cellular immune responses, which is suitable for therapeutic vaccine, while large-sized PLGA microspheres can elicit higher level of humoral immune responses, which is favorable for prophylactic HPV vaccine.

关 键 词：PLGA微球 HPV L1五聚体 粒径 免疫调控 

分 类 号：R945[医药卫生—微生物与生化药学]