Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients.

Autores de IIS La Fe

• Ana Gil Brusola

  Autor

• Santiago Pérez Tarazona

  Autor

Participantes ajenos a IIS La Fe

• Bernabeu-Gimeno, Mireia
• Pardo-Freire, Marco
• Chan, Benjamin K
• Turner, Paul E
• Carrasco-Hernandez, Laura
• Quintana-Gallego, Esther
• Domingo-Calap, Pilar

Grupos

• Infección Grave

  

  Investigador Principal

  María Ángeles Tormo Mas

• Perinatología

  

  Leader

  Máximo Vento Torres

Abstract

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 10days 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 33days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42days 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 understandclinical 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.

Keywords

• BACTERIOPHAGES