A bacteriophage based virus-like particle vaccine induces cross-reactive neutralizing antibodies against porcine epidemic diarrhea viruses (PEDV)

Although vaccines against porcine epidemic diarrhea viruses (PEDV) are available currently, PED outbreaks still occur in many countries due to emerging new variants. Therefore, more endeavors are required to develop efficient and broadly-protective vaccines. To this end, we here present a nanoparticles vaccine candidate AP205-S1 which effectively elicited antibody responses in mice and pigs. The vaccine was generated by coupling S1 protein of PEDV-KB2013, a G-II strain to bacterially expressed AP205-VLP via SpyCatcher/SpyTag. AP205-S1 demonstrated intact and homogenous viral particle structure and packed E. coli -derived ssRNA. Upon administration in mice, AP205-S1 induced high titers of S1-specific IgG antibodies in sera as well as in gastrointestinal tracts, especially after booster. Importantly, these antibodies were able to neutralize PEDV in vitro , indicating the vaccine is able to induce protective antibodies against PEDV infection. Of note, AP205-S1 elicited antibodies exhibited cross-neutralizing potential against a G-I strain, PEDV-AH2018-HF1, which was preserved in our lab. Last but not least, S1-specific IgG antibodies were stimulated in piglets after AP205-S1 immunization, which could neutralize PEDV in vitro . Most interestingly, AP205-S1 immunized piglets showed reduced viral loads compared to control piglets upon viral challenge. In conclusion, we generated a VLP-based vaccine candidate against PEDV demonstrating excellent immunogenicity in mice and piglets, which granted potential protection against viral infection. Our work provides an efficient option for prevention of future PEDV epidemics.