A divalent nanoparticle vaccine confers robust protective immunity against serotype O FMDV and SVA in pigs

The complex epidemic profile of swine infectious diseases hinders effective disease control, as separate multiple-vaccine inoculation causes excessive body stress, leading to insufficient immune responses, vaccine failure, reduced production performance and increased breeding costs. Based on our pre-established FMDV/SVA nanoparticle vaccine platform, this study screened and optimized nanoparticle antigens FMDV T_3D-LS-LOOP and SVA VP1(B)-β-VP2, developed a bivalent FMDV/SVA nanoparticle vaccine via Escherichia coli prokaryotic expression system, and systematically evaluated its immune protective efficacy and biosafety in pigs. Results showed that this bivalent vaccine induced high-level neutralizing antibodies and specific IgG responses equivalent to monovalent inactivated vaccines, with strong cross-neutralizing activity against type O FMDV Mya98/Cathay lineages. It triggered Th2-type cellular immune responses against both pathogens, building a dual immune barrier via humoral and cellular immunity synergy. The vaccine showed excellent safety with no notable adverse reactions; challenge tests confirmed it completely inhibited viral replication, dissemination and shedding, reduced tissue viral loads, blocked horizontal transmission, eliminated vesicular lesions, and provided full immune protection against both viruses. In conclusion, the prepared FMDV/SVA divalent nanoparticle vaccine elicits potent specific humoral and cellular immunity against both viruses and achieves complete immune protection. As a promising candidate for FMDV and SVA coinfection control, it offers novel strategies and technical support for integrated multi-pathogen disease prevention in pig herds.