This review explores mammalian immune responses to phages with a particular emphasis on human immune responses to therapeutic phages and their potential implications for the outcomes of phage therapy. Despite the ubiquity of phages in the human microbiome, particularly in the gut (the phageome), research on immunological mechanisms governing immune responses to both endogenous and therapeutic phages are still in their infancy. We highlight key components of the immune system that contribute to clearance of phages in vivo and examine how various factors- including patient-specific variables, treatment regimens and phage characteristics can influence immune responses and, consequently, phage pharmacokinetics during therapy. A clearer understanding of human immune responses to phages is urgently needed to inform the development of more targeted and effective personalized phage therapies-an essential step in combating the escalating threat of antimicrobial resistance.
Keywords: antiphage antibodies; immune response; phage immunogenicity; phage therapy; therapeutic phage monitoring.
© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America.