title: Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Karl D
authors.initials: KD
authors.lastname: Brune
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: Darren B
authors.initials: DB
authors.lastname: Leneghan
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: Iona J
authors.initials: IJ
authors.lastname: Brian
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Ishizuka
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.|University Institute of Immunology, University of Bern, Sahli Haus 2, Inselspital, Bern, CH-3010, Switzerland.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: Sumi
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Howarth
mesh_terms: D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D010455:Peptides; D058425:Vaccines, Virus-Like Particle