A bacteriophage-based virus-like particle vaccine induces cross-reactive neutralising antibodies against porcine epidemic diarrhoea viruses (PEDV).

Although vaccines against porcine epidemic diarrhoea viruses (PEDV) are available, PED outbreaks continue to occur in many countries due to the emergence of new variants. Therefore, further endeavours are necessary to develop efficient and broadly protective vaccines. In this context, we present a nanoparticle vaccine candidate, referred to as AP205-S1, which successfully elicited antibody responses in mice and pigs. The vaccine was created by coupling the S1 protein of PEDV-KB2013, a G-II strain, to a bacterially expressed AP205-VLP using the SpyCatcher/SpyTag system. The AP205-S1 vaccine demonstrated an intact and homogenous viral particle structure, incorporating E. coli-derived ssRNA. Upon administration in mice, AP205-S1 induced high levels of S1-specific IgG antibodies in both serum and the gastrointestinal tract, particularly following a booster dose. Importantly, these antibodies were capable of neutralising PEDV in vitro, suggesting that the vaccine can generate protective antibodies against PEDV infection. Notably, the antibodies elicited by AP205-S1 exhibited cross-neutralising potential against a G-I strain, PEDV-AH2018-HF1, which was preserved in our lab. Additionally, S1-specific IgG antibodies were stimulated in piglets following immunisation with AP205-S1, and these antibodies could neutralise PEDV in vitro. Interestingly, piglets immunised with AP205-S1 exhibited lower viral loads compared to control piglets following a viral challenge. In conclusion, we developed a VLP-based vaccine candidate against PEDV, which demonstrated excellent immunogenicity in both mice and piglets, potentially providing protection against viral infection. Our work offers an effective option for preventing future PEDV epidemics.