Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model

• DOI: 10.1038/s41467-024-47192-w
• Publication Date: 2024-04-06T15:01:40Z
• Authors: Julia D. Berkson; Claire E. Wate; Garrison B. Allen; Alyxandria M. Sch...; Kristin E. Dunbar; Michael P. Coryell; Rosa L. Sava; Yamei Gao; Jessica L. Hastie; Emily M. Smith; Charlotte R. Kenn...; Sally K. Zimmermann; Paul E. Carlson
• Keywords: Phage therapy; Siphoviridae; Myoviridae

Abstract Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of immune response on clinical effectiveness. Here, we develop mouse model assess phage treatment using cocktail five phages from Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage significantly reduces fecal bacterial loads Enterococcus. We also characterize responses elicited following administration cocktail. While minimal innate are observed after administration, two rounds induces phage-specific neutralizing antibodies accelerate clearance tissues. Interestingly, myophages in our induce more robust antibody than siphophages. This anti-phage immunity effectiveness murine model. Collectively, this study shows may be an important consideration development cocktails for therapeutic use.