Review of phage displayed peptide technologies and its potential for use in vaccine development

Summary

Development of inhibitors for methanogens, dietary, vaccination against methanogens, supplementation strategies, etc. have the potential to achieve this objective. Currently CSIRO has been using peptide phage-display technology in the Reducing Emissions from Livestock Research Program (B.CCH.1011) project to discover peptides that bind to and have antimicrobial activity against the predominant rumen methanogen Methanobrevibacter ruminantium M1. While the genomics analysis provides a rational approach to identifying cell wall targets of known function, phage display libraries have been used successfully for isolating peptides that bind to and act as antagonists towards unknown receptors on the  outer surface of microorganisms, without prior knowledge of what these receptors may be. These cell surface receptors/ molecules may be crucial for persistence, colonisation and growth of methanogens in the rumen. This technology has been used to discover inhibitory peptides to Escherichia coli and Listeria monocytogenes respectively.
 The CSIRO group have established a track record in using phage display libraries for the isolation of species-specific antimicrobial peptides including peptides against Campylobacter jejuni in poultry which is patented and CSIRO and MLA are currently in the process of evaluating a patent for the methanogen-inhibiting peptides discovered in the RELRP project. The phage-display technology could be delivered as inhibitory peptides that are synthesised as linear peptides for use as supplements in ruminants or delivered through the feed base in plants. In addition, through a vaccination based approach the peptides can be used to identify antigens and then raise antibodies against cell surface proteins that are crucial to survival of methanogens in the rumen environment. The approach does not require phage delivery of the peptide and therefore phage turn-over time is not an issue for the delivery of the peptide. 
This proposal therefore complements rather than duplicates or competes with the NZ strategy but provides Australian researchers with access to an in vivo evaluation (currently there are no facilities onshore to achieve this) and delivery pipeline for the application of methanogen-inhibiting peptides discovered in the RELRP program. The review is to be conducted by CSIRO and AgResearch NZ on behalf of MLA. The report should be circulated to MLA LPI Managers.