In Vivo Anti-Bacterial Phage Therapy through Immunological Cloaking

Phage therapy can serve as an alternative treatment to overcome antibiotic resistance, but the use of phage for anti-bacterial treatments is limited by rapid clearance from systemic circulation. Here we introduce immunologically cloaked T7 phage to reduce phagocytosis through the expression of self-peptide, derived from human CD47, on the major capsid. Self-peptide expressing T7 phage (Self-T7) suppresses up to 70% phagocytosis in vitro compared to wild-type T7 phage (WT-T7). Real-time in vivo image analysis demonstrates that Self-T7 exhibits a markedly longer blood circulation compared to WT-T7. In a mouse model of bacterial infection of intestines, the survival rate of mice is greatly increased by the intraperitoneal or intravenous injection of Self-T7, while WT-T7 only exhibited limited effects on mouse survival. This work highlights the enhanced in vivo efficacy of anti-bacterial phage therapy through the immunological cloaking of phage for suppressed phagocytosis and prolonged blood circulation.