Neutralizing antibodies are not detected against endogenous bacteriophages in their respective host

Introduction Bacteriophages are increasingly recognized as vital modulators of the human microbiome and promising candidates for alternative antimicrobial therapies. Critics raise concerns about immune neutralization with prolonged use. This study examines the presence of bacteriophages in human body fluids and assesses their interaction with autologous and heterologous serum to evaluate immune neutralization of human phage isolates. Methods Inactivation and neutralization experiments were conducted by exposing samples to neat serum and complement-inactivated serum for 1 h to assess their ability to inactivate human-origin phages. Results This finding suggests that autologous bacteriophages from human subjects are recognized as self. These phages were not inactivated by either the complement system or neutralized by either homologous or heterologous antibodies. Conclusion This finding indicates that endogenous phages may reduce worries that antibody or complement activation could inactivate them. It provides evidence that these phages might bypass antibody- or complement-induced neutralization, thereby strengthening their case for therapeutic use.