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Nanomedicine ; 37: 102438, 2021 10.
Article in English | MEDLINE | ID: covidwho-1306447


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.

Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A Virus, H5N1 Subtype/drug effects , Influenza Vaccines/immunology , Influenza in Birds/immunology , RNA/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , Birds/virology , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/therapeutic use , Humans , Influenza A Virus, H5N1 Subtype/immunology , Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza Vaccines/chemistry , Influenza Vaccines/therapeutic use , Influenza in Birds/prevention & control , Influenza in Birds/virology , Mice , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Pandemics , RNA/genetics , RNA/therapeutic use