Roadmap for Phage technologies

What are we trying to achieve and why? What is the problem we are trying to solve?

Use of virus technology to deliver improved control of infectious (bacterial, protozoal, helminths) disease.

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

Consistent research methodologies to enable evaluation of efficacy and safety on animals and comparison between groups and technologies.
Socioeconomic evaluations of industry uptake.
Efficacy – Establish range of target organisms.
Safety – for the animal as well as containment (especially in a farm environment).
Equity and equality of phage products (affordability in different countries).
Increase public acceptability.
Acceptability to the end user and understanding how they are going to be applied.
How they differ from other phage products on the market.
Regulatory challenges.
Need for dedicated phage manufacturing facility and production line of phages.
Investigating phage-kinetic (how they are distributed) in the host (especially for systemic use), with various delivery systems.
Better understanding the dynamics of the interaction between phage (pure and mixed culture), plasmids (sometimes more than one in a bacterial cells), suicide systems and bacteriocins. This for in vitro and different in vivo systems (septicaemia and gut colonisation).
Research into their ability to survive in animal and in the environment is needed.
Dosing, timing (i.e. Understanding the impact of administration in different immunity states of host, age groups) and administration for each disease (systemic versus localised).
Target and Route of administrations.
Immune response and effects of several administrations.
Understanding the relation between phage and immune system (two sides – immune system kills the phages and/or the phages also kill useful microbiota).
Knowing the target population.
Specificity of phages.
Cross reactivities between phages, target bacteria, other bacteria.
Intracellular pathogens (extra delivery systems?) and biofilms.
Complexity of phage and delivery systems.
Nutrition and survival of phages in GUT environments (host/nutrition).

What approaches could/should be taken to address the research question?

Trials using standardised model systems, dosage, and controls.
Field trials.
Determining how phages behave after they have been shed by animals.
Engagement with competent authorities (EMA/FDA) to define efficacy and safety requirements, and to validate clinical protocols for market authorisation.
Cost and benefits analysis.
Producer and producer group engagement.
Marketing and benchmarking campaigns to increase acceptability of users.
Increasingly complex systems for modelling, starting with one phage and one bacterium then adding a plasmid, then two plasmids and bacteriocins but also modelling transposons.
Encapsulations for delivery to appropriate site.
Storage and application methods (on-farm).
Study interaction of phages and the immune system using organ cultures/organ on a chip.
Organ cultures could also be used for screening in vivo using phages and the microbiota

What else needs to be done before we can solve this need?

Studies on the use of phages which have a direct effect, killing pathogens (lytic and lysogenic) or other effects such as selecting for AMR plasmid loss.
Using phages as a delivery system.
Investigating the use of antimicrobials peptides (i.e. bacteriocins, tailosins…)
Better mathematical models that can incorporate several sub-bacterial entities (phages- plasmids and bacteriocins – and possibly transposons).
Establishing best phages as the different types of phages (e.g Myoviridae) have different kinetics (very complicated phages may not be as easy to dry as they have more parts to break off).

Existing knowledge including successes and failures

Extensive (recent) literature going back to 1982.