Single dose, polymeric, microparticle based vaccines: The influence of formulation conditions on the magnitude and duration of the immune response to a protein antigen

Single dose, polymeric, microparticle based vaccines: The influence of formulation conditions on the magnitude and duration of the immune response to a protein antigen
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DOI:
10.1016/s0264-410x(96)00077-1
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发表时间:
1996-10-01
期刊:
影响因子:
5.5
通讯作者:
Davis, SS
Davis, SS
中科院分区:
医学3区
文献类型:
--
作者:
Coombes, AGA;Lavelle, EC;Davis, SS

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乳化液/溶剂蒸发产生的载卵清蛋白聚(D, l -丙交酯共乙二醇酯)[载ova - PLG]微颗粒在小鼠单次皮下(s.c)给药后刺激产生高血清IgG抗体水平,免疫反应的持续时间与载体的降解速度平行。基于缓慢吸收的PLG的配方在26周内保持相对稳定的峰值抗体水平,并在1年以上的时间内保持高滴度,其水平接近于快速吸收的ova负载颗粒的峰值反应,其持续时间较短。由空白PLG微粒和OVA简单混合制备的疫苗配方显示出低的初级免疫反应,只有通过增强才能提高。ova负载的PLG微粒子表现出大量的表面蛋白质成分,分别占慢速和快速再吸收PLG总蛋白质负载的40%和60%。这些发现表明,在单次s.c.给药后,表面蛋白持续向免疫系统呈递是诱导和长期维持高抗体效价的主要因素。版权所有爱思唯尔科学有限公司
Ovalbumin-loaded poly(D,L-lactide co-glycolide) [OVA-loaded PLG] microparticles, produced by emulsion/solvent evaporation stimulated the production of high serum IgG antibody levels after a single subcutaneous (s.c.) administration in mice and the duration of the immune response paralleled the degradation rate of the carrier. Formulations based on slow, resorbing PLG maintained relatively constant peak antibody levels for 26 weeks and high titres for over 1 year at a level approximating the peak response to the faster resorbing, OVA-loaded particles which was of lower duration. Vaccine formulations prepared by simple mixing of blank PLG microparticles and OVA exhibited low primary immune responses which were only elevated by boosting. OVA-loaded PLG microparticles exhibited a substantial surface protein component amounting to ca 40% and 60% of the total protein loading for slow resorbing and fast resorbing PLG, respectively. These findings suggest that sustained presentation of surface protein to the immune system was a major factor in the induction and long-term maintenance of high antibody titres following a single s.c. administration of OVA-loaded microparticles. Copyright (C) 1996 Elsevier Science Ltd.