ABSTRACT
Influenza viruses remain a constant global threat with significant health and socioeconomic impact every year and have the potential to cause devastating pandemics [...].
Subject(s)
Influenza in Birds/virology , Influenza, Human/virology , Orthomyxoviridae/physiology , Animals , Antibodies, Viral/immunology , Birds , Humans , Immunity , Influenza Vaccines/administration & dosage , Influenza Vaccines/genetics , Influenza Vaccines/immunology , Influenza in Birds/genetics , Influenza in Birds/immunology , Influenza in Birds/prevention & control , Influenza, Human/genetics , Influenza, Human/immunology , Influenza, Human/prevention & control , Orthomyxoviridae/genetics , VaccinationABSTRACT
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.