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首页> 外文期刊>Journal of Microencapsulation: Microcapsules Liposomes Nanoparticles Microcells Microspheres >In vitro and in vivo evaluations of PLGA microsphere vaccine formulations containing pDNA coexpressing Hepatitis B surface antigen and Interleukin-2
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In vitro and in vivo evaluations of PLGA microsphere vaccine formulations containing pDNA coexpressing Hepatitis B surface antigen and Interleukin-2

机译：含有pDNA共表达乙型肝炎表面抗原和白介素2的PLGA微球疫苗制剂的体外和体内评估

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摘要

Purpose. DNA-based vaccines encoding viral antigens have been shown to elicit immune responses in animal models. In this study, a plasmid DNA (pDNA) coexpressing the middle envelope protein of hepatitis B virus (HBV) and Interleukin-2 (IL-2) was incorporated into Poly (D,L-lactic-co-glycolic acid) (PLGA) microspheres and three different formulations were investigated for their potential as a vaccine delivery system. Methods. Emulsion solvent evaporation methods of water-in-oil-in-water (w/o/w) and oil-in-water (o/w) were used to generate three different formulations in which PLGA microspheres contained pDNA either encapsulated within or adsorbed onto the microspheres. Results. In vaccine formulation A2, prepared using the (w/o/w) method, pDNA was encapsulated within the microspheres. The other two formulations (B2 and B2a) were prepared using the (o/w) method and B2 contained pDNAs encapsulated within the microspheres while B2a contained pDNAs adsorbed onto the microspheres. pDNA loading efficiencies of A2, B2 and B2a were determined to be 15%, 25% and 45%, respectively. In vitro release of pDNAs from microspheres was evaluated for a 45-day period with no conformational changes and A2 displayed slower release than that of the B2 and B2a. When mice were immunized from anterior tibialis muscle using A2, B2 and B2a formulations containing 100 μg pDNA, antibody responses were detected for 6 months in mice sera. Conclusions. Although all PLGA microsphere formulations containing pDNA elicited antibody responses by the end of the 6th month, the antibody titers were found to be higher with B2 and B2a formulations in comparison to A2 formulation and the naked pDNA in saline.
机译：目的。编码病毒抗原的基于DNA的疫苗已显示在动物模型中引起免疫反应。在这项研究中，质粒DNA（pDNA）共表达乙型肝炎病毒（HBV）和白介素2（IL-2）的中间包膜蛋白被掺入聚（D，L-乳酸-乙醇酸）（PLGA）研究了微球和三种不同制剂作为疫苗输送系统的潜力。方法。水包油包水（w / o / w）和水包油（o / w）的乳液溶剂蒸发方法用于生成三种不同的配方，其中PLGA微球包含封装在或吸附于其中的pDNA到微球上。结果。在使用（w / o / w）方法制备的疫苗制剂A2中，pDNA被封装在微球体内。使用（o / w）方法制备另外两种制剂（B2和B2a），并且B2包含封装在微球内的pDNA，而B2a包含吸附在微球上的pDNA。确定A2，B2和B2a的pDNA装载效率分别为15％，25％和45％。在45天的时间内评估了pDNA在微球中的体外释放，没有构象变化，A2的释放比B2和B2a的释放慢。当使用含有100μgpDNA的A2，B2和B2a制剂从胫骨前肌免疫小鼠时，在小鼠血清中检测了6个月的抗体反应。结论。尽管所有含pDNA的PLGA微球制剂在第6个月末均引起抗体应答，但与A2制剂和盐水中裸露的pDNA相比，B2和B2a制剂的抗体效价更高。

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