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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.

DOI:10.1016/j.vaccine.2009.10.029
PMID:19836478
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2789185/
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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A conformationally-biased, response-selective agonist of C5a acts as a molecular adjuvant by modulating antigen processing and presentation activities of human dendritic cells.
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Surface Modification of Biodegradable Microparticles with the Novel Host-Derived Immunostimulant CPDI-02 Significantly Increases Short-Term and Long-Term Mucosal and Systemic Antibodies against Encapsulated Protein Antigen in Young Naïve Mice after Respiratory Immunization.用新型宿主衍生免疫刺激剂CPDI-02对可生物降解微粒进行表面修饰，显著提高了幼龄未免疫小鼠经呼吸道免疫后针对包封蛋白抗原的短期和长期黏膜及全身抗体水平。
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