Purpose: Influenza virus remains a serious burden to global public health. Current influenza vaccine fails to provide impeccable protection efficacy to the annual seasonal influenza and cannot offer a timely response to potential pandemic influenza. It is necessary to develop next generation influenza vaccines to solve the current dilemma. Materials and Methods: We developed a recombinant, self-assembling ferritin nanoparticle that presents the extracellular domain of the influenza hemagglutinin antigen on its surface, designated as ferritin-HA. After characterizing its structure and properties, we evaluated its capacity to trigger an immune response and offer protection against influenza virus challenge in a mouse model. Results: The recombinant ferritin-HA protein expressed in Chinese hamster ovary cells assembles into nanoparticles of a defined size. This nanoparticle vaccine enhances the uptake efficiency of Dendritic cells and promotes their maturation. Immunization with ferritin-HA nanoparticle in mice induced high levels of immunoglobulin G, hemagglutination inhibition antibodies, and microneutralization antibodies, demonstrating their stronger immunogenicity compared to current split virion vaccines. Additionally, ferritin-HA nanoparticle conferred well protection against a lethal challenge with a heterologous H3N2 influenza virus in mice. Conclusion: This study indicates that a self-assembling ferritin-HA nanoparticle has great potential for enhancing immune response and protective efficacy in mice, presenting a promising strategy for developing next generation influenza vaccine candidate.
