Antibodies specific to phage virions have been observed many times, both in animals and in humans. Phages induce the T-dependent type of immune response, which is fundamental for immunological memory and long retention of abilities to recognize and respond to foreign epitopes, as manifested by efficient induction of phage-specific IgG.  

In this work we seek to understand what are molecular determinants of phage immunogenicity. Specifically, what are immunogenic phage epitopes, located in what types of proteins, where in phage virions, and possibly linked to what characteristic phage groups?

We conducted serological profiling in humans for specific response to phageome: PhageScan. PhageScan employed a library displaying proteome-wide coverage of peptides from all types of bacteriophages (almost 3x10⁵ oligopeptides) followed by immunoprecipitation and massively parallel DNA sequencing of a library, in EU and US populations. We identified approx. 2x10⁴ oligopeptides that were recognized by human IgG (at differentiated levels), with relevant phage, protein, and source identifications.

PhageScan is the first high-throughput approach that reveals major immunogenic phage epitopes affecting human populations in a natural way, that is by a natural contact with human phageome and/or with phages circulation in the environment. This observation highlights phage groups, proteins, oligopeptides that are “highly visible” for human immune system, thus supporting efficient selection of phages for therapeutic use, and improving our understanding of natural phageomes.  

This work was supported by the National Science Centre in Poland grant no. UMO-2019/35/B/NZ7/01824.