RNA-assisted self-assembly of monomeric antigens into virus-like particles as a recombinant vaccine platform

Beom Jeung Hwang, Yohan Jang, Soon Bin Kwon, Ji Eun Yu, Jongkwan Lim, Young Hoon Roh, Baik L. Seong

Research output: Contribution to journalArticlepeer-review

Abstract

Representing highly ordered repetitive structures of antigen macromolecular assemblies, virus-like particles (VLPs) serve as a high-priority vaccine platform against emerging viral infections, as alternatives to traditional cell culture-based vaccines. RNAs can function as chaperones (Chaperna) and are extremely effective in promoting protein folding. Beyond their canonical function as translational adaptors, tRNAs may moonlight as chaperones for the kinetic control of macromolecular antigen assembly. Capitalizing on genomic RNA co-assembly in infectious virions, we present the first report of a biomimetic assembly of viral capsids that was assisted by non-viral host RNAs into genome-free, non-infectious empty particles. Here, we demonstrate the assembly of bacterially-produced soluble norovirus VP1 forming VLPs (n = 180) in vitro. A tRNA-interacting domain (tRID) was genetically fused with the VP1 capsid protein, as a tRNA docking tag, in the bacterial host to transduce chaperna function for de novo viral antigen folding. tRID/tRNA removal prompted the in vitro assembly of monomeric antigens into highly ordered repetitive structures that elicited robust protective immune responses after immunization. The chaperna-based assembly of monomeric antigens will impact the development and deployment of VLP vaccines for emerging and re-emerging viral infections.

Original languageEnglish
Article number120650
JournalBiomaterials
Volume269
DOIs
Publication statusPublished - 2021 Feb

Bibliographical note

Funding Information:
This research was supported by a grant ( 20173MFDS295-2 ) from the Ministry of Food and Drug Safety in 2020. This research was supported by a grant of the Korea Health Technology R&D Project through the KoreaHealth Industry Development Institute (KHIDI) , funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HV20C0001 ). The work was supported in part by Brain Korea 21 (BK21) FOUR program.

Publisher Copyright:
© 2021 Elsevier Ltd

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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