德国科隆大学医学院Jan Rybniker团队发现高度中和的靶向铜绿假单胞菌(PA)的人抗体。相关论文于2023年11月1日发表在《细胞》杂志上。

他们在一组慢性PA感染患者中破译了B细胞和抗体对毒力相关的III型分泌系统(T3SS)的反应。单细胞分析揭示了针对T3SS针尖蛋白PcrV的多种B细胞受体库，使单克隆抗体(mAbs)的产生消除了T3SS介导的细胞毒性。利用冷冻电镜进行的机制研究发现，表面暴露的C端PcrV表位是高度中和的单克隆抗体的靶标，对耐药PA分离物具有广泛的活性。这些抗PcrV单克隆抗体在体内与常规抗生素治疗一样有效。

他们的研究表明，慢性感染患者代表了一个来源的中和抗体，这可以被利用作为治疗针对PA。

据介绍，耐药PA对人类健康构成了新的威胁，迫切需要替代治疗方法。

附：英文原文

Title: Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa

Author: Alexander Simonis, Christoph Kreer, Alexandra Albus, Katharina Rox, Biao Yuan, Dmitriy Holzmann, Joana A. Wilms, Sylvia Zuber, Lisa Kottege, Sandra Winter, Meike Meyer, Kristin Schmitt, Henning Gruell, Sebastian J. Theobald, Anna-Maria Hellmann, Christina Meyer, Meryem Seda Ercanoglu, Nina Cramer, Antje Munder, Michael Hallek, Gerd Ftkenheuer, Manuel Koch, Harald Seifert, Ernst Rietschel, Thomas C. Marlovits, Silke van Koningsbruggen-Rietschel, Florian Klein, Jan Rybniker

Issue&Volume: 2023-11-01

Abstract: Drug-resistant Pseudomonas aeruginosa (PA) poses an emerging threat to human health with urgent need for alternative therapeuticapproaches. Here, we deciphered the B cell and antibody response to the virulence-associatedtype III secretion system (T3SS) in a cohort of patients chronically infected withPA. Single-cell analytics revealed a diverse B cell receptor repertoire directed againstthe T3SS needle-tip protein PcrV, enabling the production of monoclonal antibodies(mAbs) abrogating T3SS-mediated cytotoxicity. Mechanistic studies involving cryoelectronmicroscopy identified a surface-exposed C-terminal PcrV epitope as the target of highlyneutralizing mAbs with broad activity against drug-resistant PA isolates. These anti-PcrVmAbs were as effective as treatment with conventional antibiotics in vivo. Our study reveals that chronically infected patients represent a source of neutralizingantibodies, which can be exploited as therapeutics against PA.

DOI: 10.1016/j.cell.2023.10.002

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01084-X