Influence of protein conformation and adjuvant aggregation on the effectiveness of aluminum hydroxide adjuvant in a model alkaline phosphatase vaccine.
Influence of protein conformation and adjuvant aggregation on the effectiveness of aluminum hydroxide adjuvant in a model alkaline phosphatase vaccine.
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DOI：
10.1002/jps.21433
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发表时间：
2009-01
影响因子：
3.8
通讯作者：
Randolph, Theodore W.
中科院分区：
文献类型：
--
作者：
Clausi, Amber L.;Morin, Andrea;Carpenter, John F.;Randolph, Theodore W.
关键词：
通过向胃肠外施用的基于蛋白质的疫苗中添加铝盐佐剂来增强免疫应答的机制仍然是争论的主题。然而，已经假设佐剂表面上抗原结构的不稳定对于引发免疫应答可能是重要的。此外，已经提出，如果佐剂颗粒在施用前由于加工步骤如冷冻干燥而聚集，则对含佐剂疫苗的免疫应答降低。在这项研究中，我们测试了这些假设，并检查了小鼠模型的各种液体，冷冻干燥和喷雾冷冻干燥制剂的模型疫苗，牛肠碱性磷酸酶吸附在氢氧化铝的免疫反应。碱性磷酸酶的酶活性被用作完整天然抗原结构的敏感指标。通过控制冻干过程中的二次干燥温度，生产的疫苗具有不同水平的碱性磷酸酶酶活性和不同程度的佐剂聚集，通过粒度分布进行评估。在免疫小鼠中观察到的抗碱性磷酸酶滴度与抗原保留的酶活性和疫苗制剂的平均粒径无关。
The mechanism(s) of the enhancement of the immune response by addition of aluminum salt adjuvants to parenterally administered protein-based vaccines is still the subject of debate. It has been hypothesized, however, that destabilization of the antigen structure on the surface of the adjuvant may be important for eliciting immune response. Also, it has been suggested that immune response to adjuvanted vaccines is reduced if the adjuvant particles become aggregated before administration because of processing steps such as freeze-drying. In this study, we tested these hypotheses and examined the immune response in a murine model to various liquid, freeze-dried and spray freeze-dried formulations of a model vaccine, bovine intestinal alkaline phosphatase adsorbed on aluminum hydroxide. Enzymatic activity of the alkaline phosphatase was used as a sensitive indicator of intact native antigen structure. By manipulating the secondary drying temperature during lyophilization, vaccines were produced with varying levels of alkaline phosphatase enzymatic activity and varying degrees of adjuvant aggregation, as assessed by particle size distribution. Anti-alkaline phosphatase titers observed in immunized mice were independent of both the antigen’s retained enzymatic activity and the vaccine formulation’s mean particle diameter.
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