Synergy between Lactobacillus murinus and anti-PcrV antibody delivered in the airways to boost protection against Pseudomonas aeruginosa

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy-Methods & Clinical Development Pub Date : 2024-08-30 DOI:10.1016/j.omtm.2024.101330

Thomas Sécher, Mélanie Cortes, Chloé Boisseau, Marie-Thérèse Barba Goudiaby, Aubin Pitiot, Christelle Parent, Muriel Thomas, Nathalie Heuzé-Vourc’h

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Abstract

Therapeutic antibodies (Ab) have revolutionized the management of multiple illnesses including respiratory tract infections (RTIs). However, anti-infectious Ab displayed several limitations including antigen restrictiveness, narrowed therapeutic windows, and limited dose in the vicinity of the target when delivered by parenteral routes. Strategies enhancing further Ab-dependent containment of infection are currently needed. Here we showed that a combination of inhaled anti-infectious Ab and probiotics is an efficient formulation to protect against lung infection. Using a mouse model of Pseudomonas aeruginosa-induced pneumonia, we demonstrated a synergistic effect reducing both bacterial burden and pro-inflammatory response affording protection against primary and secondary infections. This is the first study showing that the local combination in the airways of anti-infective Ab and probiotics subverts suboptimal potency of Ab monotherapy and provides protection against respiratory pathogen.

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鼠乳杆菌与在气道中递送的抗 PcrV 抗体之间的协同作用可增强对铜绿假单胞菌的抵抗力

治疗性抗体（Ab）彻底改变了包括呼吸道感染（RTI）在内的多种疾病的治疗方法。然而，抗感染抗体有几个局限性，包括抗原限制性、治疗窗口狭窄以及通过肠外途径给药时靶点附近的剂量有限。目前需要制定策略，进一步提高抗体对感染的抑制作用。在这里，我们发现吸入抗感染抗体和益生菌的组合是一种有效的预防肺部感染的配方。我们利用铜绿假单胞菌诱发肺炎的小鼠模型，证明了减少细菌负荷和促炎反应的协同效应，可防止原发性和继发性感染。这是首次有研究表明，抗感染抗体和益生菌在气道中的局部组合颠覆了抗体单一疗法的最佳效力，并提供了对呼吸道病原体的保护。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy-Methods & Clinical Development Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.90

自引率

4.30%

发文量

163

审稿时长

12 weeks

期刊介绍： The aim of Molecular Therapy—Methods & Clinical Development is to build upon the success of Molecular Therapy in publishing important peer-reviewed methods and procedures, as well as translational advances in the broad array of fields under the molecular therapy umbrella. Topics of particular interest within the journal''s scope include: Gene vector engineering and production, Methods for targeted genome editing and engineering, Methods and technology development for cell reprogramming and directed differentiation of pluripotent cells, Methods for gene and cell vector delivery, Development of biomaterials and nanoparticles for applications in gene and cell therapy and regenerative medicine, Analysis of gene and cell vector biodistribution and tracking, Pharmacology/toxicology studies of new and next-generation vectors, Methods for cell isolation, engineering, culture, expansion, and transplantation, Cell processing, storage, and banking for therapeutic application, Preclinical and QC/QA assay development, Translational and clinical scale-up and Good Manufacturing procedures and process development, Clinical protocol development, Computational and bioinformatic methods for analysis, modeling, or visualization of biological data, Negotiating the regulatory approval process and obtaining such approval for clinical trials.

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