Vaccine properties of antigens entrapped in microparticles produced by spray-drying technique and using various polyester polymers
Vaccine properties of antigens entrapped in microparticles produced by spray-drying technique and using various polyester polymers
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DOI：
10.1016/s0264-410x(99)00427-2
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发表时间：
2000-02-14
期刊：
影响因子：
5.5
通讯作者：
Riveau, G
中科院分区：
文献类型：
--
作者：
Baras, B;Benoit, MA;Riveau, G
本研究调查了喷雾干燥技术产生的各种微粒对包埋和保存抗原的物理、化学和生物学特性的适用性。这些微粒是由具有不同相对分子质量的聚丙交酯聚合物或聚丙交酯-乙交酯共聚物组成的。以曼氏血吸虫重组28 kDa谷胱甘肽S转移酶(RSm28GST)为模型抗原，其平均粒径小于或等于5微米，抗原负载量约为2%(w/w)，经十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法分析，证实了其理化性质的保守性。包埋rSm28GST的小鼠一次腹腔免疫后，产生了高水平的抗体，免疫后至少7个月仍能产生高水平的抗体。同型图谱分析表明，免疫小鼠主要产生抗rSm28GST免疫球蛋白(Ig)G1，并伴有较低的IgG2a和IgG2b水平。最后，rSm28GST主要表位区域的识别和rSm28GST的酶活性被抗血清中和，证实了该反应针对抗原天然结构的特异性，这些结果证实了所包埋的抗原的完整性。此外，我们的结果支持这样的假设，即抗原释放的持续时间是抗体产生持续时间的限制因素。事实上，使用具有不同分子量特征的聚合物使我们能够改变免疫反应的持续时间。总之，这些结果表明，通过喷雾干燥对抗原进行微胶囊化保留了其在单剂注射后产生有效体液免疫反应所需的关键特征，(C)2000爱思唯尔科学有限公司，保留所有权利。
The present study investigated the suitability of various microparticles produced by spray-drying technique to entrap and preserve the physiochemical and biological properties of an antigen. These microparticles were constituted either by poly(lactide) polymers characterized by various molecular weight or poly(lactide-co-glycolide) polymers. The recombinant 28 kDa glutathione S-transferase of Schistosoma mansoni (rSm28GST) characterized by major epitopes involved in the active site of this enzyme was selected as model antigen, The microparticles were characterized by a mean size less than or equal to 5 mu m and an antigen loading of approximately 2% (w/w), The analysis by SDS-PAGE electrophoresis of the rSm28GST released from microparticles confirmed the conservation of its physicochemical characteristics. The conservation of the native structure of the entrapped antigen was confirmed by detecting its enzymatic activity after release from microparticles, A single intraperitoneal immunization of mice with rSm28GST entrapped in microparticles resulted in a specific antibody response, which remained high for at least 7 months, The analysis of the isotype profile indicated that immunized mice primarily produced anti-rSm28GST immunoglobulin (Ig) G1 with the coexistence of lower IgG2a and IgG2b levels. Finally, the recognition of the major epitopic regions and the neutralization of the enzymatic activity of the rSm28GST by the antisera confirmed the specificity of the response against the native structure of the antigen,These results confirmed the integrity of the entrapped antigen. Moreover, our results supported the hypothesis that the duration of antigen release is the limiting factor for the duration of antibody production. Indeed, the use of polymers characterized by different molecular weights allowed us to modify the duration of the immune response. Together, these results demonstrated that microencapsulation of an antigen by spray-drying preserved its crucial characteristics required to generate an effective humoral immune response after a single-dose administration, (C) 2000 Elsevier Science Ltd, All rights reserved.