人类中和抗体对抗SARS-CoV-2需要完整的Fc效应功能以获得最佳的治疗保护
Emma S Winkler1, Pavlo Gilchuk2, Jinsheng Yu3
1Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
Cell
|March 10, 2021
概括
中和单克隆抗体 (mAbs) 抗击SARS-CoV-2感染. 完整的mAbs对于治疗至关重要,使用Fc效应器功能通过激活单细胞和CD8+T细胞来减少炎症和肺部疾病.
科学领域:
- 免疫学
- 病毒学
- 呼吸系统医学
背景情况:
- 由SARS-CoV-2引起的COVID-19大流行凸显了有效治疗的必要性.
- 被动抗体疗法显示出有前途,但中和抗体的体内机制尚不清楚.
研究的目的:
- 在感染的动物模型中确定中和人类单克隆抗体 (mAbs) 的保护相关性.
- 阐明Fc效应器在中和mAbs的治疗效果中的作用.
主要方法:
- 使用了感染SARS-CoV-2的老鼠和仓鼠.
- 使用完整的中和mAbs与Fc功能丧失的变体mAbs.
- 进行免疫细胞耗尽 (单细胞,CD8+ T细胞).
- 分析病毒负担,肺部疾病,呼吸机制和基因表达.
主要成果:
- 对于预防而言,Fc效应器功能是不可缺少的,但对于最佳的治疗保护而言是必不可少的.
- 与Fc变异mAbs相比,完整的mAbs显著降低了病毒载量和肺病理.
- 缓解了炎症,改善了呼吸机制,并保持了组织修复.
- 单细胞和CD8+ T细胞对于中和mAbs的最大临床和病毒学益处至关重要.
结论:
- 在治疗过程中,有效中和mAbs需要Fc效应器功能,以有效地减轻SARS-CoV-2肺部感染和疾病.
- 这些功能涉及缓解炎症和促进组织修复,依赖单细胞和CD8+ T细胞.
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