人类的C. 困难特异性B细胞对保护性IgG1进行编码,尽管非中和抗体占主导地位
Sydney T Honold1, Kathleen Norris2, Jordan N May1
1Department of Microbiology and Immunology, University of Oklahoma Health Sciences, 940 Stanton L. Young Blvd., Oklahoma City, OK73104, United States.
研究人员探索了康复患者的记忆B细胞,以找到对Clostridioides difficile感染的保护性抗体. 高亲和度抗体在保护小鼠方面表现有希望,这表明了潜在的治疗途径.
科学领域:
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
- 微生物学 微生物学
背景情况:
- 困难菌感染 (CDI) 是一种严重的与医疗相关的感染,治疗有限,没有疫苗.
- Clostridioides difficile Toxin B (TcdB) 特定的IgG是预防严重和复发性CDI的关键标志物.
- 很少有针对TcdB的完全人类单克隆抗体 (hmAbs) 已经证明了治疗疗效.
研究的目的:
- 研究从康复个体中获得的记忆B细胞 (Bmem) 作为保护性抗TcdB治疗抗体的来源的潜力.
- 从Bmem衍生IgG1序列库中识别和描述高亲和度,TcdB中和的hmAbs.
主要方法:
- 从康复患者的B细胞 (Bmem) 的IgG1序列中生成一个全人类单克隆抗体 (hmAbs) 库.
- 在体外评估TcdB特异性hmAbs的结合亲和力和中和能力.
- 在体内对C57Bl/6和Tg32小鼠进行疗效研究,以评估对C. difficile引起的疾病的保护.
主要成果:
- 由Bmem衍生的抗体库包含低亲和度,非中和和高亲和度,TcdB中和 hmAbs.
- 高亲和度,TcdB中和的hmAbs在C. difficile感染的小鼠模型中显示出适度的保护.
- 在标准和人类FcRn转基因小鼠中观察到有效性,这表明肠道输送不是限制因素.
结论:
- 尽管非保护性序列占主导地位,但人类Bmem细胞是识别强效治疗性hmAbs针对C. difficile的可行来源.
- 将来自Bmem区的高亲和度中和抗体向TcdB具有治疗性潜力,用于治疗C. difficile感染.
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