Mechanisms of action of nonionic block copolymer adjuvants.
Mechanisms of action of nonionic block copolymer adjuvants.
复制标题
非离子嵌段共聚物佐剂的作用机制。
DOI：
10.1016/s0927-7765(99)00059-4
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发表时间：
1994
影响因子：
1.5
通讯作者：
A. Lal
中科院分区：
文献类型：
--
作者：
Robert L. Hunter;J. McNicholl;A. Lal
非离子型嵌段共聚物佐剂通常诱导高滴度、持久的抗体应答、细胞介导的免疫、CTL，并调节抗体的同种型和特异性。它们的主要活性是调节疏水粘附相互作用。该共聚物粘附于脂质，促进蛋白质抗原保留在表面，激活补体，并诱导巨噬细胞上II类（IA）的表达。它们产生抗原的浓缩表面基质和活化的宿主介质，其促进抗原呈递给免疫系统的细胞。共聚物佐剂与多种MDP和LPS制剂协同作用以增加总滴度，特别是IgG 2a和IgG 2b同种型的总滴度。一个令人惊讶的发现是它们通过至少两种机制影响抗体的特异性。盐水制剂和水包油（o/w）乳剂比油包水（w/o）乳剂诱导更多的针对颗粒表面上不稳定的构象依赖性表位的抗体。最后，我们发现非常大的共聚物能够稳定水包油包水（w/o/w）或多重乳液，其可以在通过上胃肠道期间保护抗原。因此，它们是用于口服递送疫苗的有吸引力的载体。
Nonionic block copolymer adjuvants typically induce high-titer, long-lasting antibody responses, cell-mediated immunity, CTLs, and modulate the isotype and specificity of antibody. Their primary activity is modulation of hydrophobic adhesive interactions. The copolymers adhere to lipids, promote retention of protein antigen to surfaces, activate complement, and induce expression of class II (IA) on macrophages. They produce a concentrated surface matrix of antigen and activated host mediators that facilitates antigen presentation to cells of the immune system. The copolymer adjuvants act synergistically with multiple MDP and LPS preparations to increase total titers, especially those of the IgG2a and IgG2b isotypes. A surprising discovery was that they influence the specificity of antibody by at least two mechanisms. Saline formulations and oil-in-water (o/w) emulsions induced more antibody against labile, conformationally dependent epitopes on the surface of particles than water-in-oil (w/o) emulsions. Finally, we found that very large copolymers are able to stabilize water-in-oil-in-water (w/o/w) or multiple emulsions that can protect antigen during passage through the upper GI tract. They are therefore attractive vehicles for oral delivery of vaccines.