A synthetic phageome reveals widespread and diverse human antibody responses to bacteriophages

A recent study has uncovered a vast and varied landscape of human antibody responses to bacteriophages, often referred to as phages. Researchers have developed a platform called PhageScan, which employs a technique called PhIP-Seq to analyze 277,051 phage and 49,630 human viral oligopeptides. This platform was used to test the antibody reactions of 192 healthy individuals who had no prior history of phage therapy.

The research revealed that nearly all donors exhibited a strong IgG reaction to phages, a finding that is comparable in prevalence and intensity to the response against human viruses. However, these antibody responses were not uniform across individuals, suggesting a high degree of individual variability. Furthermore, the study identified 12,576 peptides that were significantly enriched in the antibodies of at least two individuals, indicating a subset of phage peptides that are particularly immunogenic.

Interestingly, the most strongly immunogenic epitopes were predominantly derived from phages that infect pathogenic bacteria. In contrast, the widely shared public epitopes were more commonly found in phages associated with environmental and food-associated bacteria. This finding suggests that phages from these sources may elicit a more broadly recognized antibody response in humans.

Moreover, the study introduced ImmE, a lactococcal phage endolysin recognized in a significant majority (59.9%) of the study participants. However, the presence of sera identified as ImmE-reactive by PhageScan was found to reduce the antibacterial activity of ImmE, highlighting the functional relevance of these phage-directed antibodies.

Overall, these findings establish phage-directed antibodies as a ubiquitous component of human immunity and demonstrate the potential of PhageScan as a scalable platform for understanding the complex interactions between phages and human antibodies.