Single shot with tetanus toxoid in biodegradable microspheres protects mice despite acid-induced denaturation of the antigen
Single shot with tetanus toxoid in biodegradable microspheres protects mice despite acid-induced denaturation of the antigen
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DOI：
10.1016/s0264-410x(96)00145-4
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发表时间：
1996-12-01
期刊：
影响因子：
5.5
通讯作者：
Beuvery, EC
中科院分区：
文献类型：
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作者：
Kersten, GFA;Donders, D;Beuvery, EC
用4种不同厂家生产的可生物降解聚酯微球包裹破伤风环状疫苗，对其抗原载量、体外释放模式、抗原完整性和免疫原性进行了评价。长达140天的体外释放研究表明，只有在最初的几天里破伤风环才被释放。尽管一些制剂被设计成以脉冲式的方式释放其抗原含量，但在体外从未观察到这一点。微球中的0.3 LF破伤风环状疫苗一次免疫可引起显著的体液反应，多数情况下高于普通破伤风环状免疫，有时高于一剂明胶吸附的环状疫苗，但总是低于加强免疫。结果表明，微球制剂的中等性能(无助推效应)可能是由于酸诱导的抗原变性。尽管存在这一缺陷，但在微球免疫一次后用50LD(50)攻击一年后，小鼠的保护水平平均显著高于接受普通破伤风环状免疫的小鼠。版权所有(C)1996爱思唯尔科学有限公司。
Tetanus toroid encapsulated in microspheres consisting of biodegradable polyesters, prepared by four different manufacturers were evaluated with respect to antigenic load, in vitro release pattern, antigen integrity and immunogenicity. In vitro release studies over periods up to 140 days indicated that only during the first days tetanus toroid was released. Although some preparations were designed to release their antigen content in a pulsatile manner, this was never observed in vitro. A single immunization with 0.3 Lf tetanus toroid in microspheres induced substantial humoral responses, in most cases higher than one immunization with plain tetanus toroid, sometimes higher than one dose of alum-adsorbed toroid but always lower than booster immunizations. It is shown that the moderate (no booster effect) performance of the microsphere preparations is probably due to acid induced denaturation of the antigen. Despite this drawback, protection level in mice after challenge with 50 LD(50) 1 year after one immunization with microspheres was, on average, substantially higher than mice receiving plain tetanus toroid. Copyright (C) 1996 Elsevier Science Ltd.