Immune efficacy evaluation of a PEDV spike protein-derived multi-epitope subunit vaccine candidate in mice

Porcine epidemic diarrhea virus (PEDV)-induced piglet diarrhea remains one of the most threatening infectious diseases in the swine industry across many countries. Although commercial vaccines are available, their efficacy in preventing the incidence and prevalence of porcine epidemic diarrhea (PED) remains unsatisfactory. Here we developed three subunit vaccine candidates based on four antigenic domains of the PEDV spike (S) protein expressed in E. coli: core neutralizing epitope (COE), S1 subunit domain A (S1A), and more conservative antigenic epitopes heptad repeat 1 (HR1) and heptad repeat (HR2) in S2 protein. Vaccination of the three vaccine candidates (COE, COE-S1A, and COE-HR1-HR2) induced substantial humoral and cellular expression, as evidenced by increase in specific antibody production and mRNA expression of both Th1 and Th2 cytokines. Among them, the COE-HR1-HR2 construct demonstrated a superior outcome. Furthermore, comparative screening of immune adjuvants was conducted to optimize vaccine efficacy. CpG ODN, in combination with the COE-HR1-HR2 fusion protein, induced enhanced humoral and cellular immune responses compared with Freund's adjuvant and GEL 02, and was comparable to ISA660VG. Taken together, in view of the incomplete protection provided by current vaccines against PEDV, there is an urgent need for next-generation formulations that can effectively reduce disease burden and promote robust herd immunity. Our preliminary findings indicate that the COE-HR1-HR2 candidate, by integrating the core S1 and conserved S2 antigenic epitopes, offers the potential for developing novel multi-epitope vaccine against PEDV that could induce protective immunity thereby reducing disease development.