Invited Talk: Spy and Snoop Peptide Superglues to Empower Vaccines, Biomaterials and Antibodies

A special feature of Streptococcus pyogenes enables spontaneous isopeptide bond formation within certain cell-surface proteins. We engineered this system to generate an irreversible peptide-protein interaction (SpyTag/SpyCatcher). This system is rapid, genetically-encodable and specific in diverse biological environments. Latest advances include accelerating to infinite affinity and a toolbox of modules for rapidly controlling protein architectures. Cyclizing enzymes using SpyTag conferred resilience to boiling, for biotransformation and nutrition. SpyTag and the related superglue SnoopTag allow programmable synthesis of multi-functional teams or biomaterials, to modulate precisely cancer cell signaling. Virus-like particles (VLPs) are nano-assemblies with many attractive features for vaccination. However, decorating VLPs with antigens by genetic fusion or chemical modification is often unsuccessful. We demonstrated complete reaction to SpyCatcher-VLPs after mixing with SpyTag linked to a range of malaria antigens and cancer targets. Spy-VLPs efficiently induced antibody responses after only a single immunization and in the absence of adjuvant. Modular assembly using SpyTag should accelerate vaccine development against a range of human and veterinary diseases.