一种构象偏倚、应答选择性人 C5a 激动剂对体内和体外免疫功能的增强作用：对疫苗设计中新型佐剂的启示。
Enhancement of in vivo and in vitro immune functions by a conformationally biased, response-selective agonist of human C5a: implications for a novel adjuvant in vaccine design.
机构信息
San Diego State University BioSciences Center, 5500 Campanile Drive, San Diego, CA 92182-4650b, United States.
出版信息
Vaccine. 2009 Dec 11;28(2):463-9. doi: 10.1016/j.vaccine.2009.10.029. Epub 2009 Oct 15.
Abstract
A conformationally biased, agonist of human C5a(65-74) (EP67) was assessed for its adjuvant activities in vitro and in vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). EP67 did not induce the release of these cytokines from splenic APCs obtained from C5a receptor knockouts (CD88(-/-)). Serum from mice immunized with EP67-ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like Ab class switch. Spleen cell cultures from wild type mice but not CD88(-/-) mice showed an enhanced OVA-specific proliferative response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant.
摘要
一种人 C5a(65-74)（EP67）构象偏倚激动剂在体外和体内均被评估了其佐剂活性。EP67 诱导 C5a 受体 (CD88) 表达的抗原呈递细胞 (APC) 释放炎症 (Th1) 型细胞因子。EP67 不会从 C5a 受体敲除 (CD88(-/-)) 的脾 APC 中诱导这些细胞因子的释放。用 EP67-卵清蛋白 (OVA) 免疫的小鼠的血清中含有高 OVA 特异性抗体 (Ab) 滴度 [IgG1、IgG2a (IGg2c)、IgG2b]。单独接受 OVA 的小鼠仅产生 IgG1 Abs，表明 EP67 诱导 Th1 样 Ab 类转换的能力。来自野生型小鼠而非 CD88(-/-) 小鼠的脾细胞培养物在体外显示出增强的 OVA 特异性增殖反应。这些结果表明 EP67 能够驱动 Th1 介导的免疫反应，并且其可能作为一种独特的佐剂使用。
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