Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach.
Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach.
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DOI：
10.1016/j.jconrel.2016.11.011
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发表时间：
2016-12-28
影响因子：
10.8
通讯作者：
Reed, Steven G.
中科院分区：
文献类型：
--
作者：
Fox, Christopher B.;Orr, Mark T.;Van Hoevena, Neal;Parker, Sarah C.;Mikasa, Traci J. T.;Phan, Tony;Beebe, Elyse A.;Nana, Ghislain I.;Joshi, Sharvari W.;Tomai, Mark A.;Elvecrog, James;Fouts, Timothy R.;Reed, Steven G.
近世纪来，铝盐一直是最广泛使用的疫苗佐剂制剂，并因此建立了安全性和有效性的历史。然而，对于结核病或艾滋病毒等极具挑战性的疾病靶点，铝盐的佐剂活性可能不足以达到保护功效。TLR配体对铝盐的吸附促进增强的佐剂活性，例如在人乳头瘤病毒疫苗Cervarix®中。然而，一些TLR配体如TLR 7/8激动剂咪唑并喹啉不能有效地吸附到铝盐上。本报告描述了通过开发合成TLR 7/8配体（3 M-052）的基于脂质的纳米混悬液来解决这一挑战的制剂方法，所述合成TLR 7/8配体（3 M-052）通过所采用的辅助脂质的结构特性促进对羟基氧化铝的吸附。在免疫小鼠中，3 M-052的羟基氧化铝吸附制剂增强了对结核病和HIV疫苗抗原的抗体和TH 1型细胞免疫应答。
For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts. The present report describes a formulation approach to solving this challenge by developing a lipid-based nanosuspension of a synthetic TLR7/8 ligand (3M-052) that facilitates adsorption to aluminum oxyhydroxide via the structural properties of the helper lipid employed. In immunized mice, the aluminum oxyhydroxide-adsorbed formulation of 3M-052 enhanced antibody and TH1-type cellular immune responses to vaccine antigens for tuberculosis and HIV.
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