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Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients
Mireia Bernabéu-Gimeno1, Marco Pardo-Freire1, Benjamin K Chan2
1Institute for Integrative Systems Biology, University of Valencia-CSIC, 46980 Paterna, Spain.
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.
Insights
Nebulized phage therapy shows promise for cystic fibrosis patients with bacterial lung infections, reducing bacterial load and improving quality of life. Monitoring anti-phage antibodies is crucial for understanding long-term clinical outcomes.
Area of Science:
- Microbiology
- Immunology
- Pulmonology
Background:
- Cystic fibrosis (CF) patients frequently suffer from recurrent multidrug-resistant (MDR) bacterial lung infections.
- Phage therapy is a potential treatment for these infections, but clinical data is limited.
- Anti-phage immune responses are often overlooked, especially after non-invasive administration routes.
Purpose of the Study:
- To evaluate the clinical outcomes of nebulized monophage therapy in cystic fibrosis patients.
- To monitor bacterial load, phage persistence, and immune responses following phage therapy.
- To investigate the potential of personalized phage therapy over ready-to-use cocktails.
Main Methods:
- Three CF patients received nebulized in-house phage preparations for 10 days alongside standard antibiotics.
- Clinical indicators, bacterial counts, and phage/antibiotic susceptibility were monitored.
- Phage detection in sputum and anti-phage antibody levels in serum were assessed.
Main Results:
- Bacterial load decreased by 3-6 log in two of the three treatments.
- Phages were detected in sputum up to 33 days post-treatment.
- Phage-neutralizing antibodies were detected in all patients, marking the first report after nebulized therapy.
Conclusions:
- Nebulized phage therapy can reduce bacterial load and improve quality of life in CF patients, even without complete bacterial eradication.
- The development of anti-phage antibodies highlights the need for long-term monitoring.
- Personalized monophage therapies may be preferable to cocktails to mitigate potential adverse antibody generation.
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