抗疟疾抗体工程扩大了识别动机,并揭示了增强保护宽度的新同型相互作用
Jihwan Chun1,2, Prabhanshu Tripathi3, Yevel Flores-Garcia4
1The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA.
bioRxiv : the preprint server for biology
|November 19, 2025
概括
一种新的单克隆抗体L9_yd19通过强烈结合Plasmodium falciparum circumsporozoite蛋白 (PfCSP) 来改善疟疾保护. 这种增强的抗体为更广泛的疟疾预防策略提供了潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
- 结构生物学 结构生物学
背景情况:
- 单克隆抗体L9在非洲儿童中对疟疾提供了显著的保护.
- L9针对Plasmodium falciparum circumsporozoite蛋白 (PfCSP) 上的NVDP小重复的目标.
- 需要提高L9对具有改变重复结构的罕见寄生虫菌株的亲和力.
研究的目的:
- 为了增强L9抗体的结合亲和力.
- 为了改善对各种Plasmodium falciparum菌株的保护.
- 阐明增强抗体结合的结构机制.
主要方法:
- 网站和突变发生和酵母查,以识别L9变体.
- 在体内挑战研究使用转基因Plasmodium模型.
- 电子显微镜 (Cryo-EM) 用于确定抗体-抗原复合结构.
主要成果:
- 确定了一种亲和力改善的变体,L9_yd19.
- L9_yd19表现出对有间隔或单个小重复的Plasmodium菌株的增强效力.
- L9_yd19对NANP主要重复表现出高度亲和力,并对NANP12菌株进行保护.
- 低温电磁检测显示,L9_yd19利用双同型接口来结合PfCSP.
结论:
- L9_yd19是改善疟疾预防的有希望的候选者.
- 双同型接口机制为抗体设计提供了一个新的策略.
- 这项工作有助于开发更广泛的疟疾疫苗和治疗方法.
相关概念视频
00:42Cross-reactivity
32.8K
Overview
32.8K
01:26Antibody Actions
2.3K
Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
2.3K
01:10Antibody Structure
65.2K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.2K