Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity
Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity
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DOI：
10.1016/j.vaccine.2011.01.011
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发表时间：
2011-03-16
期刊：
影响因子：
5.5
通讯作者：
Van Mechelen, Marcelle
中科院分区：
文献类型：
--
作者：
Morel, Sandra;Didierlaurent, Arnaud;Van Mechelen, Marcelle
AS03 是一种在水包油 (o/w) 乳液中含有 α-生育酚和角鲨烯的佐剂系统 (AS)。 AS03已被考虑用于开发大流行性和季节性流感疫苗。 AS03 作用模式的主要特征在小鼠体内和人体细胞离体中进行了研究。 AS03的佐剂活性优于氢氧化铝，并且需要AS03与抗原的时空共定位。这一要求与 AS03 触发注射部位和引流淋巴结 (dLN) 短暂产生细胞因子的要求一致。产生的细胞因子的性质与 dLN 中粒细胞和负载抗原的单核细胞的增强募集一致。 AS03 中需要存在α-生育酚才能达到最高的抗体反应。 α-生育酚的存在还调节一些细胞因子的表达，包括 CCL2、CCL3、IL-6、CSF3 和 CXCL1；增加单核细胞中的抗原负荷；并增加了 dLN 中粒细胞的募集。因此，AS03促进单核细胞作为主要抗原呈递细胞，及其对粒细胞和细胞因子的影响，可能都有助于增强抗原特异性适应性免疫应答。 (C) 2011 年，爱思唯尔有限公司出版。
AS03 is an Adjuvant System (AS) containing alpha-tocopherol and squalene in an oil-in-water (o/w) emulsion. AS03 has been considered for the development of pandemic and seasonal influenza vaccines. Key features of AS03's mode of action were investigated in vivo in mice and ex vivo in human cells. AS03's adjuvant activity was superior to that of aluminium hydroxide and required the spatio-temporal co-localisation of AS03 with the antigen. This requirement coincided with AS03 triggering a transient production of cytokines at the injection site and in the draining lymph nodes (dLNs). The nature of the cytokines produced was consistent with the enhanced recruitment of granulocytes and of antigen-loaded monocytes in the dLNs. The presence of alpha-tocopherol in AS03 was required for AS03 to achieve the highest antibody response. The presence of alpha-tocopherol also modulated the expression of some cytokines, including CCL2, CCL3, IL-6, CSF3 and CXCL1; increased the antigen loading in monocytes; and increased the recruitment of granulocytes in the dLNs. Hence, AS03's promotion of monocytes as the principal antigen-presenting cells, and its effects on granulocytes and cytokines, may all contribute to enhancing the antigen-specific adaptive immune response. (C) 2011 Published by Elsevier Ltd.