Eldridge J H, Staas J K, Meulbroek J A, McGhee J R, Tice T R, Gilley R M
Department of Microbiology, University of Alabama, Birmingham 35294.
Mol Immunol. 1991 Mar;28(3):287-94. doi: 10.1016/0161-5890(91)90076-v.
The utility of biodegradable and biocompatible microspheres as a vaccine delivery system for the induction of systemic and disseminated mucosal antibody responses was investigated. Intraperitoneal (ip) injection into mice of 1-10 microns microspheres, constructed of the copolymer poly(DL-lactide-coglycolide) (DL-PLG) which contained approximately 1% by weight a formalinized toxoid vaccine of staphylococcal enterotoxin B (SEB), dramatically potentiated the circulating IgG anti-toxin antibody response as compared to the free toxoid. The initiation of vaccine release was delayed in larger microspheres, and a mixture of 1-10 and 20-50 microns microspheres stimulated both a primary and an anamnestic secondary anti-toxin response following a single injection. However, neither free nor microencapsulated SEB toxoid induced a detectable mucosal IgA anti-toxin response following systemic injection. In contrast, three peroral immunizations with toxoid-microspheres stimulated circulating IgM, IgG and IgA anti-toxin antibodies and a concurrent mucosal IgA response in saliva, gut washings and lung washings. Systemic immunization with microencapsulated toxoid primed for the induction of disseminated mucosal IgA responses by subsequent oral or intratracheal (it) boosting in microspheres, while soluble toxoid was ineffective at boosting. These results indicate that biodegradable and biocompatible microspheres represent an adjuvant system with potentially widespread application in the induction of both circulating and mucosal immunity.
研究了可生物降解且具有生物相容性的微球作为疫苗递送系统诱导全身和弥散性黏膜抗体反应的效用。将由聚（DL-丙交酯-乙交酯）（DL-PLG）共聚物构建的1-10微米微球腹腔注射到小鼠体内，该微球含有约1%重量的经福尔马林处理的葡萄球菌肠毒素B（SEB）类毒素疫苗，与游离类毒素相比，显著增强了循环IgG抗毒素抗体反应。较大微球中疫苗释放的起始延迟，1-10微米和20-50微米微球的混合物在单次注射后刺激了初次和回忆性二次抗毒素反应。然而，全身注射后，游离或微囊化的SEB类毒素均未诱导出可检测到的黏膜IgA抗毒素反应。相比之下，用类毒素微球进行三次口服免疫刺激了循环IgM、IgG和IgA抗毒素抗体，并在唾液、肠道冲洗液和肺冲洗液中同时引发了黏膜IgA反应。用微囊化类毒素进行全身免疫，为随后通过微球口服或气管内（it）加强免疫诱导弥散性黏膜IgA反应做好准备，而可溶性类毒素在加强免疫方面无效。这些结果表明，可生物降解且具有生物相容性的微球代表了一种佐剂系统，在诱导循环免疫和黏膜免疫方面可能具有广泛的应用。
