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Neutralizing antibody response against subcutaneously injected bacteriophages in rabbit model
Archana Archana1, Prem Shankar Patel2, Rajesh Kumar1
1Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India.
Virusdisease
|May 10, 2021
Summary
Bacteriophage therapy efficacy can be limited by neutralizing antibodies. This study in rabbits showed antibodies rise after 3 weeks, suggesting bacteriophages are best for acute bacterial infections (<2 weeks). For longer treatments, consider phage cocktails.
Area of Science:
- Microbiology
- Immunology
- Therapeutic Biotechnology
Background:
- Bacteriophage therapy is a promising alternative to antibiotics.
- The development of neutralizing anti-phage antibodies can hinder therapeutic success.
- Understanding antibody response is crucial for optimizing bacteriophage treatment strategies.
Purpose of the Study:
- To investigate the induction of neutralizing antibodies following parenteral bacteriophage administration in an animal model.
- To determine the kinetics of antibody response and its impact on bacteriophage neutralization.
- To inform the clinical application of bacteriophage therapy based on treatment duration.
Main Methods:
- Isolation, purification, and characterization of bacteriophages against five key bacterial pathogens.
- Subcutaneous weekly administration of bacteriophages (10^9 PFU) to rabbits over six weeks.
- Weekly blood sampling and analysis of anti-phage antibody response using phage neutralization assays and plaque assays.
Main Results:
- A significant rise in neutralizing anti-phage antibodies was observed starting around the third week post-immunization.
- Complete bacteriophage neutralization was achieved between 3 and 5 weeks.
- Elevated bacteriophage counts were noted at higher serum dilutions by week 6, with background antibodies against E. coli phages.
- Antibody response varied among different bacteriophages, with no significant response against four out of five tested.
Conclusions:
- Parenteral bacteriophage administration induces neutralizing antibody production in mammalian hosts.
- The timing and duration of bacteriophage therapy are critical factors influencing treatment efficacy due to antibody development.
- Bacteriophage therapy is suitable for acute bacterial infections (<2 weeks); prolonged therapy may necessitate phage cocktails with diverse antigenicity.
