通过鼻子输送IgM可提供广泛的SARS-CoV-2变种保护
Zhiqiang Ku1, Xuping Xie2, Paul R Hinton3
1Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Nature
|June 3, 2021
概括
研究人员设计了一种免疫球蛋白M (IgM) 抗体,即IgM-14,其效果比IgG对抗SARS-CoV-2的效果大230倍. 这种新型IgM抗体有效中和耐药变体,并为COVID-19治疗提供了有前途的鼻内预防和治疗潜力.
科学领域:
- 免疫学
- 病毒学
- 药理学
背景情况:
- 抗体耐药性对有效的COVID-19治疗构成重大挑战.
- 现有的免疫球蛋白G (IgG) 疗法由于病毒耐药性而面临限制.
- 开发强大的中和抗体对于对抗SARS-CoV-2至关重要.
研究的目的:
- 设计一种新的免疫球蛋白M (IgM) 中和抗体 (IgM-14),以克服基于IgG的疗法所遇到的抗性.
- 评估IgM-14对SARS-CoV-2及其变种的有效性和中和能力.
- 在临床前模型中评估注射IgM-14的预防和治疗效果.
主要方法:
- 来自父母的IgG抗体的免疫球蛋白M (IgM-14) 中和抗体的工程.
- 在实验室中对SARS-CoV-2进行中和测试,包括耐药变种和受体结合域突变.
- 在小鼠的体内疗效研究中,使用鼻内药物进行预防和治疗.
- 在动物中注射IgM-14的药理动力学和安全性分析.
主要成果:
- 与其母体IgG-14相比,IgM-14在中和SARS-CoV-2方面表现出超过230倍的功效.
- IgM-14有效中和了耐药的SARS-CoV-2变种 (阿尔法,贝塔,玛) 和其他21种受体结合域突变.
- 单次注射IgM-14在小鼠中具有预防和治疗效果,优于IgG-14对特定变异的效果.
- 在动物模型中,鼻内IgM-14表现出良好的药理动力学和安全性.
结论:
- 设计的IgM抗体,如IgM-14,可以显著提高中和效能,克服对SARS-CoV-2的抗性.
- 最佳的表位选择对于最大限度地提高工程IgM抗体的疗效至关重要.
- 鼻内注射IgM-14为简化和有效的预防和治疗COVID-19提供了有希望的策略,包括对抗性菌株的治疗.
相关概念视频
01:22Development of Immunocompetence
548
The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
548
01:15Transcytosis of IgG
3.5K
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
3.5K