A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody

Abstract

Protein-based self-assembling nanoplatforms exhibit superior immunogenicity compared with soluble antigens. Here, we present a comprehensive vaccine strategy for displaying classical swine fever virus (CSFV) E2 glycoprotein on the surface of ferritin (fe) nanocages. An E2-specific blocking antibody assay showed that the blocking rates in <i>p</i>E2-fe/Gel02 (84.3%) and a half-dose cohort of E2-fe/Gel02 (81.9%) were significantly higher (<i>p</i> < 0.05) than that in a ferritin-free cohort of <i>p</i>E2/Gel02 (62.7%) at 21 days post immunization (dpi) in vivo. Furthermore, quantitation of neutralizing potency revealed that a highly significant difference (<i>p</i> < 0.001) was observed between the <i>p</i>E2-fe/Gel02 cohort (1:32, equivalent to live-attenuated strain C at 1:32) and the <i>p</i>E2/Gel02 cohort (1:4) at 21 dpi. Moreover, the innate immune cytokines of IL-4 and IFN-γ activated by the half-dose (20 μg) cohort of E2-fe/Gel02 were equivalent to those elicited by the full dose (40 μg) of purified E2 in the <i>p</i>E2/Gel02 cohort at most time points. In conclusion, we successfully obtained an antigen-displaying E2-ferritin nanoplatform and confirmed high ferritin-assisted humoral and cellular immunities. Our results provided a novel paradigm of self-assembling nanovaccine development for the defense and elimination of potentially pandemic infectious viral pathogens.