Fragments of the bacterial cell wall peptidoglycan, murein, have long been known to have potent adjuvant properties. The murein component N-acetylmuramylalanyl-d-isoglutamine (MDP) has been shown to functionally substitute for killed mycobacteria in Freund's Complete Adjuvant, and the repeating unit of murein, N-acetylglucosaminyl-1,4-N-acetylmuramylalanyl-d-isoglutamine (glucosaminylmuramyl dipeptide, GMDP) has an even stronger immunomodulatory activity than MDP. Synthetic versions of these molecules and other murein-component derivatives have been extensively studied as potential adjuvants for human use, but significant side effects such as pyrogenicity and uveitis have prevented their acceptance for clinical use.
Scientists have recently developed a method for isolating peptides that have similar biophysical properties to a given target molecule. The peptides were isolated by using a GMDP-specific antibody to screen a phage-display library, selecting for peptides that mimic the biochemical properties and/or the biophysical shape of the GMDP molecule.
Using this technique, a set of peptides has been generated and individual members shown to stimulate significantly larger antibody responses to ovalbumin than the parent GMDP molecule in a mouse model, but with no evidence of pyrogenic side-effects.

Innovative Aspects:
" Peptides mimicking GMDP (one of the most active components of bacterial cell wall-based adjuvants) can be isolated, retaining the properties of GMDP, but without any associated pyrogenic effects;" Peptides have potent non-specific immunostimulatory properties;" They have been shown to significantly protect against a lethal challenge with live coliform bacteria in an animal model.

 

Patents/Rights: Patent(s) applied for but not yet granted

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