A Multiepitope Nanovaccine Candidate Adjuvanted with Porcine Ferritin Scaffold for African Swine Fever Virus

<b>Background</b>: African swine fever (ASF) is a highly contagious acute febrile disease with a near 100% mortality rate. There are currently no safe and effective vaccines for this disease. Cellular immunity plays an important role in the process of anti-viral, activating an effective cellular immune response is a prerequisite for the effectiveness of the vaccine. <b>Methods</b>: To effectively activate cellular immune responses, 133 immunodominant T cell epitopes (TEPs) were identified and synthesized into ten recombinant multi-epitope proteins (MEPs). These MEPs were subsequently conjugated to porcine ferritin (pFTH1) to generate MEPs-pFTH1 nanoparticles. Animal experiments were conducted to evaluate their immunogenicity and biocompatibility. <b>Results</b>: Animal experiments demonstrated that both MEPs and MEPs-pFTH1 nanoparticles induced significant humoral and cellular immune responses. Compared to MEPs monomers, the MEPs-pFTH1 nanoparticles induced a 10- to 100-fold increase in IgG and IgG2a antibody titers (<i>p</i> < 0.05), as well as a significantly higher number of IFN-γ⁺ cells. Serum from pigs immunized with MEPs-pFTH1 nanoparticles can significantly inhibit ASFV replication. <b>Conclusions</b>: Our novel self-assembled porcine ferritin nanovaccine candidate can induce strong humoral and cellular immune responses in swine and mice that effectively inhibit ASFV replication. Therefore, the nanovaccine is a highly biocompatible and safe candidate vaccine for ASF that warrants further investigation, such as conducting animal challenge experiments to evaluate the effectiveness of the vaccine.