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

Sci Rep. 2016 Jan 19:6:19234. doi: 10.1038/srep19234.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Bacteriophages / genetics
  • Bacteriophages / immunology
  • Capsid / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Escherichia coli / genetics
  • Humans
  • Peptides / genetics
  • Peptides / immunology*
  • Vaccination
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*

Substances

  • Antigens, Viral
  • Capsid Proteins
  • Peptides
  • Vaccines, Virus-Like Particle