Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display

Sci Adv. 2019 Sep 25;5(9):eaaw2853. doi: 10.1126/sciadv.aaw2853. eCollection 2019 Sep.

Abstract

Self-assembling virus-like particles represent highly attractive tools for developing next-generation vaccines and protein therapeutics. We created ADDomer, an adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold engineered to facilitate plug-and-play display of multiple immunogenic epitopes from pathogens. We used cryo-electron microscopy at near-atomic resolution and implemented novel, cost-effective, high-performance cloud computing to reveal architectural features in unprecedented detail. We analyzed ADDomer interaction with components of the immune system and developed a promising first-in-kind ADDomer-based vaccine candidate to combat emerging Chikungunya infectious disease, exemplifying the potential of our approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae* / classification
  • Adenoviridae* / genetics
  • Adenoviridae* / immunology
  • Communicable Disease Control
  • Communicable Diseases / etiology
  • Communicable Diseases / immunology
  • Epitope Mapping / methods*
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology*
  • Genetic Engineering
  • Humans
  • Models, Molecular
  • Nanomedicine
  • Nanotechnology
  • Protein Conformation
  • Structure-Activity Relationship
  • Vaccination
  • Vaccines, Synthetic / immunology*
  • Vaccinology / methods
  • Viral Proteins / chemical synthesis
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Epitopes
  • Vaccines, Synthetic
  • Viral Proteins