Controlled release microparticles as a single dose diphtheria toxoid vaccine: immunogenicity in small animal models

被引:44
作者
Singh, M
Li, XM
Wang, HY
McGee, JP
Zamb, T
Koff, W
Wang, CY
O'Hagan, DT
机构
[1] Chiron Corp, Emeryville, CA 94608 USA
[2] United Biomed Inc, Hauppauge, NY 11788 USA
[3] Core Technol Ltd, Hannah Res Inst, Ayr KA6 5HL, Scotland
关键词
diphtheria toxoid; controlled release; microparticles; vaccine delivery;
D O I
10.1016/S0264-410X(97)80912-7
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Diphtheria toxoid (DT) was encapsulated in microparticles prepared from polylactide-co-glycolide (PLG) polymers using a solvent evaporation technique. Combinations of small and large size 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 that 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 adsorbed 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. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:346 / 352
页数:7
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