Bacterial superglues, spontaneous amide bond formation, and nano-assemblies to tickle the immune system

Professor Mark Howarth, University of Oxford. RSC Norman Heatley Award Seminar.

A special feature of the bacterium Streptococcus pyogenes enables spontaneous isopeptide bond formation within particular proteins. We have re-engineered this chemistry to generate an irreversible peptide-protein interaction (SpyTag/SpyCatcher). This reaction is rapid, genetically-encodable and specific in diverse biological environments. Cyclizing enzymes using SpyTag conferred resilience to boiling, as may be applicable for enhancing animal dietary supplementation. SpyTag and its related superglue SnoopTag allows programmable synthesis of multi-functional teams, to modulate precisely cancer cell signalling. Virus-like particles (VLPs) are nano-assemblies with many attractive features for vaccination. However, decorating VLPs with target antigens by genetic fusion or chemical modification is often unsuccessful. We demonstrated 100% reaction to SpyCatcher-VLPs after mixing with SpyTag linked to a range of malaria antigens and cancer peptides. Spy-VLPs efficiently induced antibody responses after only a single immunization and without adjuvant. Plug-and-display VLP decoration has potential to accelerate vaccine development against a range of human and veterinary diseases.

For further information contact: Mike Webb