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

Julia D. Berkson, Claire E. Wate, Garrison B. Allen, Alyxandria M. Schubert, Kristin E. Dunbar, Michael P. Coryell, Rosa L. Sava, Yamei Gao, Jessica L. Hastie, Emily M. Smith, Charlotte R. Kenneally, Sally K. Zimmermann and Paul E. Carlson ()
Additional contact information
Julia D. Berkson: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Claire E. Wate: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Garrison B. Allen: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Alyxandria M. Schubert: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Kristin E. Dunbar: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Michael P. Coryell: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Rosa L. Sava: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Yamei Gao: Office of Vaccines Research and Review, Division of Viral Products, Laboratory of Pediatric and Respiratory Viral Diseases
Jessica L. Hastie: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Emily M. Smith: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Charlotte R. Kenneally: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Sally K. Zimmermann: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology
Paul E. Carlson: Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47192-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47192-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47192-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().