Mechanism of immunopotentiation and safety of aluminum adjuvants.
Mechanism of immunopotentiation and safety of aluminum adjuvants.
复制标题
铝佐剂的免疫原理和安全机制。
DOI：
10.3389/fimmu.2012.00406
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发表时间：
2012
影响因子：
7.3
通讯作者：
Hogenesch H
中科院分区：
文献类型：
--
作者：
Hogenesch H
含铝佐剂广泛应用于传染病预防性疫苗和过敏免疫治疗制剂中。它们增强免疫反应的机制仍然知之甚少。铝佐剂注射小鼠后选择性地刺激 Th2 免疫反应，并在人类中刺激混合反应。它们支持 CD8 T 细胞的激活，但这些细胞不会终末分化为细胞毒性 T 细胞。铝佐剂吸附抗原，通过促进吞噬作用和减缓抗原从注射部位的扩散来增强免疫反应，从而为炎症细胞积累提供时间。吸附强度很重要，因为高亲和力相互作用会干扰免疫反应。吸附还会影响抗原的物理和化学稳定性。铝佐剂通过直接和间接机制激活树突状细胞。铝佐剂的吞噬作用随后破坏吞噬溶酶体，激活 NLRP3 炎症小体，导致活性 IL-1β 和 IL-18 的释放。铝佐剂还通过与膜脂筏结合来激活树突状细胞。注射铝佐剂疫苗会导致受损细胞释放尿酸、DNA 和 ATP，从而激活树突状细胞。铝佐剂的使用因细胞介导的免疫刺激较弱而受到限制。这可以通过添加其他免疫调节分子来增强。这些分子的吸附由控制抗原吸附的相同机制决定，并且可以影响此类组合佐剂的功效。铝佐剂的广泛使用部分归功于基于 70 年使用历史的出色安全记录。它们会引起注射部位的局部炎症，但也会通过结合疫苗中的生物活性分子来减轻全身和局部反应的严重程度。
Aluminum-containing adjuvants are widely used in preventive vaccines against infectious diseases and in preparations for allergy immunotherapy. The mechanism by which they enhance the immune response remains poorly understood. Aluminum adjuvants selectively stimulate a Th2 immune response upon injection of mice and a mixed response in human beings. They support activation of CD8 T cells, but these cells do not undergo terminal differentiation to cytotoxic T cells. Adsorption of antigens to aluminum adjuvants enhances the immune response by facilitating phagocytosis and slowing the diffusion of antigens from the injection site which allows time for inflammatory cells to accumulate. The adsorptive strength is important as high affinity interactions interfere with the immune response. Adsorption can also affect the physical and chemical stability of antigens. Aluminum adjuvants activate dendritic cells via direct and indirect mechanisms. Phagocytosis of aluminum adjuvants followed by disruption of the phagolysosome activates NLRP3-inflammasomes resulting in the release of active IL-1β and IL-18. Aluminum adjuvants also activate dendritic cells by binding to membrane lipid rafts. Injection of aluminum-adjuvanted vaccines causes the release of uric acid, DNA, and ATP from damaged cells which in turn activate dendritic cells. The use of aluminum adjuvant is limited by weak stimulation of cell-mediated immunity. This can be enhanced by addition of other immunomodulatory molecules. Adsorption of these molecules is determined by the same mechanisms that control adsorption of antigens and can affect the efficacy of such combination adjuvants. The widespread use of aluminum adjuvants can be attributed in part to the excellent safety record based on a 70-year history of use. They cause local inflammation at the injection site, but also reduce the severity of systemic and local reactions by binding biologically active molecules in vaccines.
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DOI：
10.1084/jem.20021910
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Curtsinger JM;Lins DC;Mescher MF
通讯作者：
Mescher MF
影响因子：
4.4
作者：
Comoy, EE;Capron, A;Thyphronitis, G
通讯作者：
Thyphronitis, G
影响因子：
5.5
作者：
Day, M. J.;Schoon, H.-A.;Thibault, J.-C.
通讯作者：
Thibault, J.-C.
影响因子：
5.4
作者：
Cunningham, AF;Serre, K;MacLennan, ICM
通讯作者：
MacLennan, ICM
影响因子：
5.5
作者：
DILLON, SB;DEMUTH, SG;HANNA, N
通讯作者：
HANNA, N