Enhancing humoral and mucosal immune response of PED vaccine candidate by fusing S1 protein to nanoparticle multimerization

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen with a high mortality rate, which poses a serious threat to newborn piglets. A rapid, safe and effective vaccine is necessary for protecting pigs from PED infection. Nanoparticles have become molecular scaffolds for displaying soluble antigens due to their unique physical and chemical properties. Here, a vaccine candidate was based on the display of PEDV S1 protein on a mi3 nanoparticle platform using SpyTag/SpyCatcher technology. The size, zeta potential and microstructure of the S1-mi3 NPs were investigated, and their effects on the uptake of antigen-presenting cells (APCs) and maturation of dendritic cells (DCs) were analyzed. Mice were immunized via muscular and intranasal administrations, and the levels of humoral, cellular and mucosal immune responses were analyzed. As a result, S1 proteins were surface-displayed on NPs successfully, which self-assembled into nanoparticles composed of 60 subunits and showed superior safety and stability. In addition, mi3 NPs promoted antigen internalization and dendritic cell (DCs) maturation. In the mouse model, S1-mi3 NPs significantly increased the PEDV-specific antibody including serum IgG, secretory IgA (SIgA) and neutralizing antibodies (NAb). Furthermore, S1-mi3 NPs elicited more CD3+CD4+ and CD3+CD8+ T cell and cellular immune-related cytokines (IFN-γ and IL-4) compared to monomeric S1. In particular, it can induce an effective germinal center-specific (GC) B cell response, which is closely related to the production of neutralizing antibodies. Overall, S1-mi3 NPs are a promising subunit vaccine candidate against PEDV, and this self-assembly NPs also provide an attractive platform for improving vaccine efficacy against emerging pathogens.