疟疾疫苗无法诱导其序列内的保护性表位的抗体
Y Charoenvit1, W E Collins, T R Jones
1Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20889.
Science (New York, N.Y.)
|February 8, 1991
概括
开发有效的Plasmodium vivax疟疾亚单元疫苗需要针对特定的保护性表位. 用Plasmodium vivax circumsporozoite蛋白重复疫苗接种并没有给予保护,这凸显了微调免疫反应的必要性.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 寄生虫学的寄生虫学
背景情况:
- 活型疟原体 (Plasmodium vivax circumsporozoite,简称CS) 蛋白质是疟疾疫苗的一个关键标.
- 以前的疫苗策略集中在CS蛋白内重复的表位上.
研究的目的:
- 为了评估基于P. vivax CS蛋白重复的复合子单位疫苗的疗效.
- 调查特异性表位识别在对P.vivax疟疾的保护性免疫力中的作用.
主要方法:
- 赛米里被免疫的重组蛋白含有20个副本的P. vivax CS蛋白重复.
- 子被挑战使用P. vivax sporozoites以评估疫苗的疗效.
- 单克隆抗体NVS3,保护性对脊髓菌挑战,被用于表位图映射.
主要成果:
- 用CS蛋白重复免疫诱导高抗体标位,但未能预防P. vivax挑战.
- 接受保护性单克隆抗体NVS3的子显示出对虫诱导的疟疾有显著的保护.
- 皮层映射显示,NVS3在CS蛋白重复中识别了一种特定的四氨基酸序列 (AGDR),而这种序列并不是疫苗诱导的抗体的目标.
结论:
- 针对整个CS蛋白重复的抗体不足以保护P. vivax疟疾.
- 免疫反应的精细特异性,特别是对AGDR表位的识别,对于有效的亚单元疫苗设计至关重要.
- 未来的P.vivax疫苗开发应该集中在引起针对AGDR.等特定保护性表位的抗体上.
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