Singh M, Li X M, Wang H, McGee J P, Zamb T, Koff W, Wang C Y, O'Hagan D T
Chiron Corporation, Emeryville, CA 94608, USA.
Vaccine. 1998 Feb;16(4):346-52. doi: 10.1016/s0264-410x(97)80912-7.
Diphtheria toxoid (DT) was encapsulated in microparticles prepared from polylactide-co-glycolide (PLG) polymers using a solvent evaporation technique. Combinations of small and large sized microparticles with controlled release characteristics were used to immunize Sprague Dawley rats and the antibody responses were monitored for one year. For comparison, control groups of rats were immunized at 0, 1 and 2 months with DT adsorbed to alum. The antibody responses generated by the microparticles were comparable to the alum immunized control groups from 32 weeks. Microparticles with a single entrapped antigen (DT) induced better antibody responses than microparticles with two antigens entrapped simultaneously (DT + TT). Microparticles prepared from a single polymer were less effective for long term antibody induction than a combination of microparticles prepared from three different polymers. A combination vaccine consisting of antigen absorbed to alum and also entrapped in microparticles gave the best response. In an inhibition assay designed to determine the relative binding of antisera to the antigen, the sera from the microparticle and the alum immunized animals showed comparable binding. An intradermal challenge study was performed in rabbits, which showed similar levels for the alum and the microparticle immunized animals at 4, 12 and 32 weeks after immunization.
使用溶剂蒸发技术将白喉类毒素（DT）包裹在由聚丙交酯-乙交酯（PLG）聚合物制备的微粒中。使用具有控释特性的大小微粒组合对斯普拉格-道利大鼠进行免疫，并监测一年的抗体反应。作为对照，对照组大鼠在第0、1和2个月用吸附于明矾的DT进行免疫。从第32周起，微粒产生的抗体反应与明矾免疫对照组相当。包埋单一抗原（DT）的微粒比同时包埋两种抗原（DT + TT）的微粒诱导出更好的抗体反应。由单一聚合物制备的微粒在长期抗体诱导方面比由三种不同聚合物制备的微粒组合效果更差。由吸附于明矾且包埋在微粒中的抗原组成的联合疫苗产生的反应最佳。在旨在确定抗血清与抗原相对结合的抑制试验中，微粒免疫动物和明矾免疫动物的血清显示出相当的结合。在兔子身上进行了皮内攻毒研究，结果显示免疫后第4、12和32周，明矾免疫动物和微粒免疫动物的水平相似。
