Spike 1 trimer, a nanoparticle vaccine against porcine epidemic diarrhea virus induces protective immunity challenge in piglets

Porcine epidemic diarrhea virus (PEDV) is considered the cause for porcine epidemic diarrhea (PED) outbreaks and hefty losses in pig farming. However, no effective commercial vaccines against PEDV mutant strains are available nowadays. Here, we constructed three native-like trimeric candidate nanovaccines, i.e., spike 1 trimer (S1-Trimer), collagenase equivalent domain trimer (COE-Trimer), and receptor-binding domain trimer (RBD-Trimer) for PEDV based on Trimer-Tag technology. And evaluated its physical properties and immune efficacy. The result showed that the candidate nanovaccines were safe for mice and pregnant sows, and no animal death or miscarriage occurred in our study. S1-Trimer showed stable physical properties, high cell uptake rate and receptor affinity. In the mouse, sow and piglet models, immunization of S1-Trimer induced high-level of humoral immunity containing PEDV-specific IgG and IgA. S1-Trimer-driven mucosal IgA responses and systemic IgG responses exhibited high titers of virus neutralizing antibodies (NAbs) in vitro. S1-Trimer induced Th1-biased cellular immune responses in mice. Moreover, the piglets from the S1-Trimer and inactivated vaccine groups displayed significantly fewer microscopic lesions in the intestinal tissue, with only one and two piglets showing mild diarrhea. The viral load in feces and intestines from the S1-Trimer and inactivated vaccine groups were significantly lower than those of the PBS group. For the first time, our data demonstrated the protective efficacy of Trimer-Tag-based nanovaccines used for PEDV. The S1-Trimer developed in this study was a competitive vaccine candidate, and Trimer-Tag may be an important platform for the rapid production of safe and effective subunit vaccines in the future.