Self-Assembled Nanoparticle Vaccines Elicit Robust Protective Immune Responses against Type O Foot-and-Mouth Disease Virus Infection

Foot-and-mouth disease virus (FMDV), a critical pathogen in the global livestock industry, has long been a focal point of international disease control strategies. This study developed a nanoparticle-based FMDV vaccine platform. We fused the FMDV immunodominant epitope (VP1-G-H-loop) and T-cell epitope (T_3D) with the nanoparticle scaffold <i>lumazine synthase</i> (LS), efficiently producing the T_3D-LS-LOOP nanoparticle vaccine using the prokaryotic expression system <i>Escherichia coli</i> (BL21). Mouse experiments showed that the T_3D-LS-LOOP nanoparticle vaccine induced a more robust immune response than the LS-LOOP nanoparticle vaccine. To evaluate the role of different scaffolds in FMDV antigen presentation, we substituted the LS scaffold with Ferritin (Ft) and β-<i>annulus</i> peptide (β) nanoparticles, generating T_3D-β-LOOP and T_3D-Ft-LOOP nanoparticle proteins. The results demonstrated that the LS scaffold-mediated T_3D-LS-LOOP nanoparticle vaccine induced the highest neutralizing antibody (NAb) titers (1:2^8.5) and an effective T-cell immune response, providing 100% protection in mice, outperforming T_3D-Ft-LOOP (66.7%) and T_3D-β-LOOP (83.3%) nanoparticle vaccines. Encouragingly, the T_3D-LS-LOOP nanoparticle vaccine also induced high NAb titers against different lineages (Mya98/Cathay/PanAsia) of type O FMDV and a strong Th2-biased cellular immune response in swine, with no adverse reactions observed postvaccination, achieving complete protection against a type O FMDV challenge in swine.