Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization

• Published in: Scientific reports Vol. 6; no. 1; p. 19234
• Main Authors: Brune, Karl D, Leneghan, Darren B, Brian, Iona J, Ishizuka, Andrew S, Bachmann, Martin F, Draper, Simon J, Biswas, Sumi, Howarth, Mark
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 19.01.2016
• Subjects: Antigens; Antigens, Viral - genetics; Antigens, Viral - immunology; Bacteriophages - genetics; Bacteriophages - immunology; Cancer; Capsid - immunology; Capsid Proteins - genetics; Capsid Proteins - immunology; Chemical modification; Epidermal growth factor; Escherichia coli - genetics; Humans; Malaria; Nanoparticles; Peptides - genetics; Peptides - immunology; Telomerase; Vaccination; Vaccine development; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - immunology; Virus-like particles
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep19234

Virus-like particles (VLPs) are non-infectious self-assembling nanoparticles, useful in medicine and nanotechnology. Their repetitive molecularly-defined architecture is attractive for engineering multivalency, notably for vaccination. However, decorating VLPs with target-antigens by genetic fusion or chemical modification is time-consuming and often leads to capsid misassembly or antigen misfolding, hindering generation of protective immunity. Here we establish a platform for irreversibly decorating VLPs simply by mixing with protein antigen. SpyCatcher is a genetically-encoded protein designed to spontaneously form a covalent bond to its peptide-partner SpyTag. We expressed in E. coli VLPs from the bacteriophage AP205 genetically fused to SpyCatcher. We demonstrated quantitative covalent coupling to SpyCatcher-VLPs after mixing with SpyTag-linked to malaria antigens, including CIDR and Pfs25. In addition, we showed coupling to the VLPs for peptides relevant to cancer from epidermal growth factor receptor and telomerase. Injecting SpyCatcher-VLPs decorated with a malarial antigen efficiently induced antibody responses after only a single immunization. This simple, efficient and modular decoration of nanoparticles should accelerate vaccine development, as well as other applications of nanoparticle devices.