Ferritin nanoparticles displaying rift valley fever virus glycoprotein elicit potent dendritic cell activation in vitro

Abstract Rift Valley fever (RVF) is a mosquito-borne zoonosis of major concern for human and animal health, yet no licensed human vaccine exists. Here, we engineered a self-assembling nanoparticle vaccine candidate by genetically fusing the RVF virus glycoprotein Gn to the N-terminus of a hybrid bacterial ferritin, generating nanoparticles that display 24 copies of Gn on their surface. Cryo-electron microscopy at 6 Å resolution confirmed ordered and symmetric presentation of the antigens, consistent with the structural models of ferritin and Gn. When incubated with human monocyte-derived dendritic cells, the Gn-ferritin nanoparticles were efficiently internalized and induced robust expression of maturation markers (e.g., CD54, CD83, CD86) and secretion of pro-inflammatory cytokines (e.g., IL-1β, IL-6, IL-12p40, TNF-α), in contrast to soluble Gn or ferritin controls. These findings demonstrate that ferritin nanoparticles provide a structurally defined and immunologically active platform for RVF virus antigen display, establishing a foundation for the development of safe and effective subunit vaccines against this emerging pathogen. Graphical Abstract