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

Berkson, Julia D.; Wate, Claire E.; Allen, Garrison B.; Schubert, Alyxandria M.; Dunbar, Kristin E.; Coryell, Michael P.; Sava, Rosa L.; Gao, Yamei; Hastie, Jessica L.; Smith, Emily M.; Kenneally, Charlotte R.; Zimmermann, Sally K.; Carlson, Paul E.

doi:10.1038/s41467-024-47192-w

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

Journal Article · 06 April 2024 · Nature Communications

DOI: https://doi.org/10.1038/s41467-024-47192-w · OSTI ID:2471357

Berkson, Julia D. ^[1]; Wate, Claire E. ^[1]; Allen, Garrison B. ^[1]; Schubert, Alyxandria M. ^[1];

^[1]; Coryell, Michael P. ^[1];

^[1]; Gao, Yamei ^[1]; Hastie, Jessica L. ^[1]; Smith, Emily M. ^[1]; Kenneally, Charlotte R. ^[1];

^[1];

^[1]

US Food and Drug Administration (USFDA), Silver Spring, MD (United States). Center for Biologics Evaluation and Research

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

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Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: National Institute of Allergy and Infectious Diseases (NIAID); USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2471357

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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