...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of peptide science: An official publication of the European Peptide Society >Aldehyde modification and alum coadjuvancy enhance anti-TNF-alpha autovaccination and mitigate arthritis in rat
【24h】

Aldehyde modification and alum coadjuvancy enhance anti-TNF-alpha autovaccination and mitigate arthritis in rat

机译：醛修饰和明矾共佐剂可增强大鼠的抗TNF-α自身免疫接种并减轻关节炎

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Experimental vaccination to induce antibodies (Abs) capable of cytokine antagonism shows promise as a novel immunotherapy for chronic inflammatory disease. We prepared a hybrid antigen consisting of residues 141-235 of rat TNF- fused to the C-terminus of glutathione-S-transferase (GST), chemically modified to incorporate aldehyde residues, for development of an auto-vaccine eliciting anti-rTNF- Abs. In rat immunization the soluble aldehyde-modified fusion protein did not generate observable Ab responses. By contrast, vaccination with the aldehyde-modified fusion protein adsorbed on alum induced anti-TNF- autoAbs with high titer and neutralizing activity. Induction of adjuvant arthritis in rats pre-immunized with unmodified fusion protein or a control protein in alum resulted in severe inflammation and joint damage, whereas the disease induced in rats immunized with the aldehyde-bearing fusion protein in alum was markedly attenuated. Similar results were obtained in a collagen-induced rat arthritis model. Anti-collagen II IgG Ab titers did not deviate significantly in groups pre-immunized with modified fusion protein and control protein, suggesting that anti-TNF vaccination did not skew the immune response related to disease induction. This study demonstrates synergy between particulate alum and protein bound carbonyl residues for enhancement of protein immunogenicity. The antigen-specific co-adjuvant system could prove advantageous for breaking tolerance in emerging auto-vaccination therapies targeting inflammatory cytokines as well as for enhancing a broader category of subunit vaccines. Aldehyde adduction introduces a minimal modification which, together with the established use of alum as a safe adjuvant for human use, could be favorable for further vaccine development. Copyright (c) 2014 European Peptide Society and John Wiley & Sons, Ltd.
机译：实验证明，能够诱导细胞因子拮抗作用的抗体（Abs）的疫苗接种有望作为一种针对慢性炎症疾病的新型免疫疗法。我们制备了一种杂种抗原，该杂种抗原由大鼠TNF-的141-235位残基与谷胱甘肽S-转移酶（GST）的C末端融合而成，经过化学修饰以掺入醛基残基，用于开发自动疫苗引发的抗rTNF-吸收在大鼠免疫中，可溶性醛修饰的融合蛋白未产生可观察到的抗体应答。相反，用吸附在明矾上的醛修饰的融合蛋白进行的疫苗接种具有高滴度和中和活性。在明矾中用未修饰的融合蛋白或对照蛋白预免疫的大鼠中诱导佐剂性关节炎会导致严重的炎症和关节损伤，而在明矾中用含醛的融合蛋白免疫的大鼠中诱发的疾病明显减弱。在胶原诱导的大鼠关节炎模型中获得了相似的结果。在使用修饰的融合蛋白和对照蛋白进行预免疫的组中，抗胶原蛋白II IgG抗体滴度没有显着偏离，这表明抗TNF疫苗接种不会使与疾病诱导相关的免疫反应产生偏差。这项研究表明颗粒明矾和蛋白质结合的羰基残基之间的协同作用可增强蛋白质的免疫原性。抗原特异性共佐剂系统可证明有利于打破新兴的针对炎性细胞因子的自体免疫疗法的耐受性，以及增强更广泛种类的亚单位疫苗。醛加合物引入了最小的修饰，再加上明矾作为人类安全佐剂的确定用途，可能有利于进一步的疫苗开发。版权所有（c）2014欧洲肽学会和John Wiley＆Sons，Ltd.

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号