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Nanomedicine . RNA-dependent assembly of chimeric antigen nanoparticles as an efficient H5N1 pre-pandemic vaccine platform

tetano

Editor, Senior Moderator
Nanomedicine


. 2021 Jul 10;102438.
doi: 10.1016/j.nano.2021.102438. Online ahead of print.
RNA-dependent assembly of chimeric antigen nanoparticles as an efficient H5N1 pre-pandemic vaccine platform


Jongkwan Lim[SUP] 1 [/SUP], Yucheol Cheong[SUP] 1 [/SUP], Young-Seok Kim[SUP] 1 [/SUP], Wonil Chae[SUP] 1 [/SUP], Beom Jeung Hwang[SUP] 1 [/SUP], Jinhee Lee[SUP] 2 [/SUP], Yo Han Jang[SUP] 3 [/SUP], Young Hoon Roh[SUP] 4 [/SUP], Sang-Uk Seo[SUP] 5 [/SUP], Baik L Seong[SUP] 6 [/SUP]



Affiliations

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) pose a significant threat to human health, with high mortality rates and require effective vaccines. We showed that, harnessed with novel RNA-mediated chaperone function, hemagglutinin (HA) of H5N1 HPAIV could be displayed as an immunologically relevant conformation on self-assembled chimeric nanoparticles (cNP). A tri-partite monomeric antigen was designed including: i) an RNA-interaction domain (RID) as a docking tag for RNA to enable chaperna function (chaperna: chaperone + RNA), ii) globular head domain (gd) of HA as a target antigen, and iii) ferritin as a scaffold for 24 mer-assembly. The immunization of mice with the nanoparticles (~46 nm) induced a 25-30 fold higher neutralizing capacity of the antibody and provided cross-protection from homologous and heterologous lethal challenges. This study suggests that cNP assembly is conducive to eliciting antibodies against the conserved region in HA, providing potent and broad protective efficacy.

Keywords: chaperna; ferritin nanoparticle; hemagglutinin; influenza vaccine; self-assembly.
 
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