Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters

Nipah virus (NiV) is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans. Here, based on self-assembled ferritin nanoparticles (FeNPs), we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG (residues 71-602, FeNP-sG) and G_head (residues 182-602, FeNP-G_head) onto E. coli-expressed FeNPs (FeNP-sG and FeNP-G_head, respectively) through Spycatcher/Spytag technology. Compared with sG and G_head alone, FeNP-sG and FeNP-G_head elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice, whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-G_head group. These results further demonstrate that sG possesses greater antigenicity than G_head and that FeNPs can dramatically enhance immunogenicity. Furthermore, FeNP-sG provided 100% protection against NiV challenge in a hamster model when it was administered twice at a dose of 5 μg/per animal. Our study provides not only a promising candidate vaccine against NiV, but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.