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    Repetitive exposure to bacteriophage cocktails against Pseudomonas aeruginosa or Escherichia coli provokes marginal humoral immunity in naïve mice (2023)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Weissfuss, Chantal
    Wienhold, Sandra-Maria
    Bürkle, Magdalena
    Gaborieau, Baptiste
    Bushe, Judith (WE 12)
    Behrendt, Ulrike
    Bischoff, Romina
    Korf, Imke H. E.
    Wienecke, Sarah
    Dannheim, Antonia
    Ziehr, Holger
    Rohde, Christine
    Gruber, Achim D. (WE 12)
    Ricard, Jean-Damien
    Debarbieux, Laurent
    Witzenrath, Martin
    Nouailles, Geraldine
    Quelle
    Viruses
    Bandzählung: 15
    Heftzählung: 2
    Seiten: Artikel 387
    ISSN: 1999-4915
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://www.mdpi.com/1999-4915/15/2/387
    DOI: 10.3390/v15020387
    Pubmed: 36851601
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    14163 Berlin
    +49 30 838 62450
    pathologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Phage therapy of ventilator-associated pneumonia (VAP) is of great interest due to the rising incidence of multidrug-resistant bacterial pathogens. However, natural or therapy-induced immunity against therapeutic phages remains a potential concern. In this study, we investigated the innate and adaptive immune responses to two different phage cocktails targeting either Pseudomonas aeruginosa or Escherichia coli-two VAP-associated pathogens-in naïve mice without the confounding effects of a bacterial infection. Active or UV-inactivated phage cocktails or buffers were injected intraperitoneally daily for 7 days in C57BL/6J wild-type mice. Blood cell analysis, flow cytometry analysis, assessment of phage distribution and histopathological analysis of spleens were performed at 6 h, 10 days and 21 days after treatment start. Phages reached the lungs and although the phage cocktails were slightly immunogenic, phage injections were well tolerated without obvious adverse effects. No signs of activation of innate or adaptive immune cells were observed; however, both active phage cocktails elicited a minimal humoral response with secretion of phage-specific antibodies. Our findings show that even repetitive injections lead only to a minimal innate and adaptive immune response in naïve mice and suggest that systemic phage treatment is thus potentially suitable for treating bacterial lung infections.