Ferritin and Encapsulin Nanoparticles Enhance Immunogenicity of p30 Protein for ASFV Vaccine Development

African swine fever (ASF) represents a significant threat to the global swine industry due to the absence of a commercially available vaccine. The rational design of vaccine antigens is crucial for improving vaccine efficacy and guiding its development. The p30 protein of the African swine fever virus (ASFV) is an early membrane protein involved in the viral invasion of host cells. Antibodies against p30 effectively block viral internalization, highlighting its potential as a key vaccine antigen. In this study, ferritin and encapsulin nanoparticle platforms were utilized to display the p30 protein on their surfaces. The F/E-p30 nanoparticles significantly enhanced both the antigenicity and immunogenicity of the p30 protein. <i>In vivo</i> experiments revealed that the p30 protein, conjugated onto nanoparticles, accumulated in follicular dendritic cells (FDCs) within lymph nodes. This accumulation resulted in an increased number of T follicular helper (Tfh) and germinal center B (GCB) cells, thereby promoting the activation and maturation of both B and T cells. Compared to the p30 monomer, the p30 nanoparticles elicited stronger immune responses and facilitated the production of more potent, broad-spectrum antibodies that more effectively inhibit the internalization of genotype II and I/II recombinant ASFV strains. The p30-conjugated nanoparticles developed in this study present a competitive advantage as nanoparticle antigens, providing a robust foundation for ASFV vaccine development.