Coombes A G, Lavelle E C, Jenkins P G, Davis S S
Department of Pharmaceutical Sciences, University of Nottingham, University Park, UK.
Vaccine. 1996 Oct;14(15):1429-38. doi: 10.1016/s0264-410x(96)00077-1.
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.
通过乳液/溶剂蒸发法制备的负载卵清蛋白的聚（D，L-丙交酯乙交酯）[负载OVA的PLG]微粒，在小鼠单次皮下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率平行。基于缓慢吸收的PLG的制剂在26周内维持相对恒定的峰值抗体水平，并在超过1年的时间内保持高滴度，其水平接近对快速吸收的负载OVA微粒的峰值反应，但其持续时间较短。通过简单混合空白PLG微粒和OVA制备的疫苗制剂表现出低的初次免疫反应，仅通过加强免疫才能提高。负载OVA的PLG微粒分别表现出大量的表面蛋白成分，对于缓慢吸收和快速吸收的PLG，其分别占总蛋白负载量的约40%和60%。这些发现表明，在单次皮下给药负载OVA的微粒后，向免疫系统持续呈现表面蛋白是诱导和长期维持高抗体滴度的主要因素。
