BIODEGRADABLE AND BIOCOMPATIBLE POLY(DL-LACTIDE-CO-GLYCOLIDE) MICROSPHERES AS AN ADJUVANT FOR STAPHYLOCOCCAL ENTEROTOXIN-B TOXOID WHICH ENHANCES THE LEVEL OF TOXIN-NEUTRALIZING ANTIBODIES
BIODEGRADABLE AND BIOCOMPATIBLE POLY(DL-LACTIDE-CO-GLYCOLIDE) MICROSPHERES AS AN ADJUVANT FOR STAPHYLOCOCCAL ENTEROTOXIN-B TOXOID WHICH ENHANCES THE LEVEL OF TOXIN-NEUTRALIZING ANTIBODIES
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DOI：
10.1128/iai.59.9.2978-2986.1991
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发表时间：
1991-09-01
影响因子：
3.1
通讯作者：
GILLEY, RM
中科院分区：
文献类型：
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作者：
ELDRIDGE, JH;STAAS, JK;GILLEY, RM
研究了由具有生物相容性、可生物降解的聚乳酸-羟基乙酸酯（DL-PLG）和葡萄球菌肠毒素B （SEB）类毒素组成的微球作为疫苗递送系统皮下注射小鼠的效果。通过循环免疫球蛋白G （IgG）抗毒素滴度测量，通过直径为1至10 μ m的DL-PLG微球递送SEB类毒素，诱导的免疫反应约为未包裹类毒素的500倍。微囊化类毒素诱导的抗毒素反应的动力学、强度和持续时间与等量的类毒素乳剂（含完全的弗氏佐剂）相似。然而，微球没有诱导炎症和肉芽肿的形成，而完全的弗氏佐剂。微球的佐剂活性不依赖于SEB毒素的超抗原性，并且在响应微胶囊化三硝基苯锁眼帽贝血青素时，同样有效地增强循环IgG抗三硝基苯水平。空DL-PLG微球不具有有丝分裂性，与空DL-PLG微球混合注射SEB类毒素作为免疫原并不比单独注射类毒素更有效。直径为1 ~ 10 μ m的含抗原微球比直径为10 μ m的含抗原微球表现出更强的佐剂活性，这与直径为1 ~ 10 μ m的含抗原微球进入巨噬细胞内的引流淋巴结有关，而与直径为10 μ m的含抗原微球不相关。微囊化SEB类毒素免疫诱导的抗体应答对静脉注射毒素引起的体重减轻和脾脏v - β -8+ t细胞扩增具有保护作用。这些结果表明，由药学上可接受的组分组成的DL-PLG微球疫苗递送系统对其包裹的抗原具有很强的佐剂活性。
Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10-mu-m in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10-mu-m in diameter exhibited stronger adjuvant activity than those > 10-mu-m, which correlated with the delivery of the 1- to 10-mu-m, but not the > 10-mu-m, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V-beta-8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens.