囊性纤维化患者接受雾化噬菌体疗法后产生的中和抗体。

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Med Pub Date : 2024-09-13 Epub Date: 2024-06-24 DOI:10.1016/j.medj.2024.05.017
Mireia Bernabéu-Gimeno, Marco Pardo-Freire, Benjamin K Chan, Paul E Turner, Ana Gil-Brusola, Santiago Pérez-Tarazona, Laura Carrasco-Hernández, Esther Quintana-Gallego, Pilar Domingo-Calap
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引用次数: 0

摘要

背景:囊性纤维化(CF)患者容易反复发生多重耐药(MDR)细菌肺部感染。在这种情况下,噬菌体疗法被认为是一种很有前景的工具。然而,报道的病例数量有限,妨碍了对临床结果的了解。抗噬菌体免疫反应往往被忽视,只有在侵入性给药途径后才有描述:方法:针对囊性纤维化患者的金黄色葡萄球菌和/或铜绿假单胞菌肺部感染进行了三次单噬菌体治疗。在使用标准抗生素的 10 天内,对内部噬菌体制剂进行雾化吸入。对临床指标、细菌计数、噬菌体和抗生素敏感性、噬菌体检测和免疫反应进行了监测:结果:在两种治疗方法中,细菌量减少了 3-6 log。无不良反应。噬菌体在治疗结束后的 33 天内仍留在痰中。在所有病例中,治疗后 10 到 42 天的血清中都检测到了噬菌体中和抗体,这是首次报道雾化疗法后出现抗噬菌体抗体:结论:雾化噬菌体疗法减少了细菌负荷,即使没有根除细菌,也能改善生活质量。抗体的出现强调了长期监测对更好地了解临床结果的重要性。这些发现鼓励使用个性化的单噬菌体疗法,而不是即用型鸡尾酒疗法,后者可能会诱发不良抗体的产生:本研究得到了西班牙科学、创新和大学部、巴伦西亚大区以及西班牙囊性纤维化基金会合作的众筹支持。
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Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients.

Background: Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration.

Methods: Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored.

Findings: Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy.

Conclusions: Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation.

Funding: This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation.

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来源期刊
Med
Med MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
17.70
自引率
0.60%
发文量
102
期刊介绍: Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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