内注射的IgM可以保护抗原上不同的A型流感病毒亚型
Ashwin Kumar Ramesh1, Jwala Priyadarsini Sivaccumar1, Xiaohua Ye1,2
1Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Nature communications
|April 29, 2025
概括
将流感抗体工程化成IgM形式,增强它们对抗各种流感菌株的效力. 这种多价值方法提供了更广泛的保护和更好的中和,即使对抗性流感A病毒亚型.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 生物技术是生物技术.
背景情况:
- 广泛中和的单克隆抗体 (mAbs) 针对流感A病毒 (IAV) 血质素 (HA) 是对流感干预的有希望的.
- HA的可塑性会导致耐药菌株,从而损害双价IgG抗体的效力.
- 将抗IAV抗体多元化为IgM可能会增强中和的广度和效力.
研究的目的:
- 设计和评估18种IgM抗体,这些抗体来自于对各种IAV HA表位体的广泛中和IgG.
- 评估这些针对H1N1和H3N2 IAV菌株的工程IgM抗体的范围和中和力.
- 研究工程IgM的鼻内输送的潜力,以预防IAV的预防性保护.
主要方法:
- 从已知的广泛中和的抗IAV IgG 来构建18种IgM抗体,以不同的HA表位为目标.
- 在体外对各种H1N1和H3N2 IAV菌株的中和幅度和强度的评估.
- 在小鼠模型中评估工程IgM-F045-092的鼻内输送,生物保留和保护功效.
主要成果:
- 与其父母IgG相比,IgG F045-092的IgM版本表现出更大的广度和功效.
- 设计的IgM抗体通过扩大性克服了IAV菌株耐药性,实现了亚纳米分子中和.
- 在小鼠体内注射IgM-F045-092显示有效的生物保留和对致命的IAV挑战的保护.
结论:
- 作为IgM的抗IAV抗体的多重化显著提高了对各种IAV亚型的中和功效和范围.
- 工程化IgM抗体,特别是IgM-F045-092,通过克服抗菌株的抗性,为抗击流感提供了一个有希望的策略.
- 经过工程设计的IgM抗体的鼻内输送提供了对流感的有效预防性保护,突出了它们的治疗潜力.
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