Bacteriophage based therapies and immunotherapy for a post-Antibiotic era

By

Prof. Hari Mohan Saxena

Published on
October 15, 2025

National Level Monitor, DAHD, Ministry of Fisheries, Animal Husbandry & Dairying.

Areas of Expertise
Immunotherapy & Phage Biology, Diagnostics Innovation, Therapeutic Advances

The growing resistance of bacteria to antimicrobial agents worldwide presents a serious challenge. While antibiotic resistance continues to rise, development of new antibiotics is slow and resource-intensive. Bacteriophages are viruses capable of selectively eliminating specific bacteria. They replicate in bacteria as long as the target bacteria are present in the host. They offer an alternative cost effective treatment for bacterial infections in both humans and animals. Bacteriophages can infect their target bacteria without adversely affecting the normal microbial flora. The replication process continues until the targeted pathogen is completely eliminated. In the absence of their target bacteria, bacteriophages exist as simple, non-living entities composed of protein-coated DNA. Lytic bacteriophages replicate within live bacterial cells and lyse the bacteria without affecting other bacterial species. Phage lysed bacterial preparations are highly immunogenic and exhibit greater protective efficacy compared to regular vaccines produced by heat or chemical inactivation. Phage lysates have been shown to be non-toxic and safe for immunization without adverse reactions. The self-replicating nature and specificity of bacteriophages in targeting bacteria makes them choicest alternative to antibiotics.

The use of bacteriophages is a practical strategy for managing important bacterial diseases. Clinical trials in animals and humans have demonstrated that phages are safe and well-tolerated. Phages have the potential to cure bacterial infections and eliminate carrier states in both animals and humans. Live attenuated vaccine organisms can serve as a carrier vehicle to deliver phages to phagocytes in the body where virulent pathogens evade antibodies and immune cells. Once engulfed along with the attenuated organisms, the phage lyses the vaccine organism and is released inside the phagocyte, subsequently infecting and lysing the virulent pathogenic organisms.

We have employed Brucellaphages for therapy in Brucellosis-affected cattle in three ways – Phage alone, phage targeted in vivo employing attenuated bacteria as a carrier, and phage lysate. Our study on simple phage therapy showed that phage stimulates immune responses in host. In another study, we employed live attenuated B. abortus vaccine organisms to deliver a lytic Brucellaphage in vivo, targeting intracellular virulent Brucella organisms. The phage-pulsed organisms induced significantly high titers of anti-Brucella antibodies. We have also reported successful immunotherapy of bovine Brucellosis using phage lysates of attenuated B. abortus organisms.

Experience with phage based therapies confirm their promise as an alternative to antibiotics and must be supported, strengthened and promoted urgently at global level for empowering humanity to face the impending catastrophe of antimicrobial resistance.

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