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Engineering the ADDomer Nanoparticle Vaccine Scaffold for Improved Assembly and Enhanced Stability - PubMed

6 hours ago
  • #Nanoparticle Vaccines
  • #Protein Engineering
  • #Virus-like Particles
  • The ADDomer is a synthetic dodecahedral VLP scaffold derived from human adenovirus serotype 3 (Ad3) penton base protein (PBP).
  • Two engineering strategies were employed: using a Chimpanzee adenovirus Y25-based ADDomer (CHIMPSELS) to avoid preexisting immunity and introducing intersubunit disulfide bonds for stability.
  • High-resolution electron cryo-microscopy confirmed the formation of stable dodecahedral particles with disulfide bonds stabilizing PBP N-termini conformations.
  • Disulfide-stabilized ADDomers showed improved thermal stability and higher aggregation onset temperatures, useful for vaccine development screening.
  • The modified scaffolds successfully displayed immunogenic epitopes, including SARS-CoV-2 and Chikungunya peptides, maintaining structural integrity.
  • The study presents a versatile, thermostable VLP platform with reduced preexisting immunity susceptibility and modular epitope presentation capacity.