Characterisation of the immunogenic potential of therapeutic bacteriophages

Although bacteriophage therapy has significant potential to revolutionise the treatment of infection from antimicrobial resistant (AMR) pathogens, there are several critical gaps in the current knowledge [1]. One such gap is their interaction with the immune system and especially the antibodies. This is particularly important in the context of bacteriophage therapy [2]. In addition, due to the co-evolution of the phages and their microbial hosts there is the possibility that antibody cross-reactivity between phages and microbes might contribute to how patients respond [3]. Characterising immunogenic epitopes of phages and their potential for cross-reactivity with the microbiome (including the virome) will impact our understanding of how phage “specific” immune responses may affect phage therapy and will provide useful information for the design of phage cocktails [4].

Here the Centre for Phage Research will combine forces with the Institute of Precision medicine and the Institute for Structural and Chemical Biology to modify and further develop a high-resolution and high throughput analytical pipeline for the identification of exposed amino acid sequences (epitopes) in the capsid of medically promising phages from our extensive phage biobank [5]. In collaboration with the Leicester van Geest Multi-OMICs Facility, the generated data will be used to guide the development of Mass spectrometry (MS) assays to detect phage-specific and cross-reactive neutralising antibodies [6].

This pioneering analytical system will provide confidence to doctors that phages are safe and effective guiding the choice of phages and when to change specific phages during the treatment of infectious disease. In addition, it will significantly promote our understanding on the immune-phage interactions within the context of the human microbiome and virome.