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Updated: Jun 29, 2025
Author Spotlight: Investigating Bacteriophage-Induced Immune Responses in Gnotobiotic Mice
Published on: January 26, 2024
Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine
Julia D Berkson1, Claire E Wate1, Garrison B Allen1
1Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, Division of Bacterial Parasitic and Allergenic Products, Laboratory of Mucosal Pathogens and Cellular Immunology, 10903 New Hampshire Ave, Silver Spring, MD, 20832, USA.
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.
Insights
Bacteriophage therapy shows promise for antimicrobial infections. However, the study found that the host immune response, specifically neutralizing antibodies, can reduce phage cocktail effectiveness in mice.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Antimicrobial resistance is a growing global health threat.
- Bacteriophage therapy offers a potential alternative to antibiotics.
- The impact of host immune responses on phage therapy efficacy remains unclear.
Purpose of the Study:
- To develop a murine model to evaluate bacteriophage therapy efficacy.
- To investigate the immune responses elicited by a phage cocktail.
- To determine if anti-phage immunity affects therapeutic outcomes.
Main Methods:
- A mouse model was established to study Vancomycin-Resistant Enterococcus (VRE) gut colonization.
- A five-phage cocktail (Myoviridae and Siphoviridae families) was administered.
- Fecal VRE loads, phage clearance, and host immune responses (antibody production) were analyzed.
Main Results:
- Phage treatment significantly reduced VRE fecal loads.
- Repeated phage administration induced specific neutralizing antibodies against the phages.
- Myophages elicited a stronger antibody response than siphophages.
- Anti-phage antibodies reduced the therapeutic effectiveness of the phage cocktail in mice.
Conclusions:
- Phage-specific immune responses, particularly neutralizing antibodies, can diminish the clinical effectiveness of bacteriophage therapy.
- The type of phage (e.g., Myoviridae vs. Siphoviridae) influences the magnitude of the immune response.
- Consideration of host immune responses is crucial for designing effective phage-based therapeutics.
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