Disparate adjuvant properties among three formulations of "alum".
Disparate adjuvant properties among three formulations of "alum".
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DOI：
10.1016/j.vaccine.2012.11.044
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发表时间：
2013-01-11
期刊：
影响因子：
5.5
通讯作者：
Kelsoe, Garnett
中科院分区：
文献类型：
--
作者：
Cain, Derek W.;Sanders, Sergio E.;Cunningham, Michael M.;Kelsoe, Garnett
铝佐剂，通常被称为“明矾”，是人类疫苗中最广泛使用的免疫刺激剂。虽然促进对铝吸附抗原的体液反应的机制仍然是谜，但明矾被认为可以形成抗原仓库并诱导炎症信号，进而促进抗体的产生。最近有人指出，Imject®明矾，一种通常用于动物研究的商业含铝佐剂，不是人类疫苗中存在的铝佐剂的物理化学等同物。这种差异引起了人们对在动物研究中使用Imject®明矾作为已批准的铝佐剂模型的担忧。在这里，我们比较了Imject®明矾、Alhydrogel®和传统的铝抗原沉淀物诱导小鼠对半抗原载体抗原NP-CGG[（4-羟基-3-硝基苯基）乙酰鸡γ-球蛋白]的体液反应的能力。Alhydrogel®和沉淀明矾诱导的体液反应明显大于Imject®明矾诱导的。不同明矾制剂引起的体液反应强度与诱导的促炎细胞因子的数量和免疫部位炎症细胞的数量有关。此外，与Alhydrogel®和沉淀明矾相比，Imject®对蛋白抗原的吸附能力严重降低。这些发现揭示了不同的明矾制剂在免疫刺激特性上的实质性差异，这是评估新型佐剂、评估新的铝基疫苗和佐剂机制研究的一个重要考虑点。
Aluminum adjuvants, commonly referred to as “alum,” are the most widespread immunostimulants in human vaccines. Although the mechanisms that promote humoral responses to alum-adsorbed antigens are still enigmatic, alum is thought to form antigen depots and induce inflammatory signals that, in turn, promote antibody production. It was recently noted that Imject® alum, a commercial aluminum-containing adjuvant commonly used in animal studies, is not the physicochemical equivalent of aluminum adjuvant present in human vaccines. This difference raises concerns about the use of Imject® alum in animal research as a model for approved aluminum adjuvants. Here, we compared the capacity of Imject® alum, Alhydrogel®, and a traditional alum-antigen precipitate to induce humoral responses in mice to the hapten-carrier antigen, NP-CGG [(4-hydroxy-3-nitrophenyl)acetyl-chicken γ-globulin]. The magnitude of humoral responses elicited by Alhydrogel® and precipitated alum was significantly greater than that induced by Imject® alum. The strength of the humoral responses elicited by different alum formulations was correlated with the quantity of pro-inflammatory cytokines induced and the numbers of inflammatory cells at the site of immunization. Moreover, Imject® exhibited a severely reduced capacity to adsorb protein antigens compared to Alhydrogel® and precipitated alum. These findings reveal substantial differences in the immunostimulatory properties of distinct alum preparations, an important point of consideration for the evaluation of novel adjuvants, the assessment of new alum-based vaccines, and in mechanistic studies of adjuvanticity.
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