A novel recombinant S-based subunit vaccine induces protective immunity against porcine deltacoronavirus challenge in piglets

ABSTRACT Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes diarrhea in piglets and possesses the potential to infect humans. However, there are no commercially available vaccines for PDCoV. In this study, the immune responses to the spike (S) protein and receptor-binding domain (RBD) trimer were examined in mice. Neutralization assays and flow cytometry analysis demonstrated that S protein elicited more robust neutralizing antibodies (NAbs) and cellular immune responses than the RBD trimer. Spike protein and inactivated vaccine were used in the assessment of immunogenicity in piglets and sows. Immunized piglets, sows, and suckling pig showed high NAb titers and S-specific sIgA in colostrum, milk, and serum. The piglets/suckling pig from the immunized group displayed significantly fewer microscopic lesions in the intestinal tissue, with only one or no piglet showing mild diarrhea. However, all piglets/suckling pig showed mild to watery diarrhea and exhibited a high level of viral shedding in the challenged control group. The feces from the piglets/suckling pig in the S protein and inactivated vaccine group exhibited reduced viral load. Of note, vaccine-elicited NAbs last for more than 4 months in immunized piglets. Together, our data demonstrate for the first time the protective efficacy of S-based subunit vaccine, which could be a candidate vaccine against PDCoV. IMPORTANCE As an emerging porcine enteropathogenic coronavirus that has the potential to infect humans, porcine deltacoronavirus (PDCoV) is receiving increasing attention. However, no effective commercially available vaccines against this virus are available. In this work, we designed a spike (S) protein and receptor-binding domain (RBD) trimer as a candidate PDCoV subunit vaccine. We demonstrated that S protein induced more robust humoral and cellular immune responses than the RBD trimer in mice. Furthermore, the protective efficacy of the S protein was compared with that of inactivated PDCoV vaccines in piglets and sows. Of note, the immunized piglets and suckling pig showed a high level of NAbs and were associated with reduced virus shedding and mild diarrhea, and the high level of NAbs was maintained for at least 4 months. Importantly, we demonstrated that S protein-based subunit vaccines conferred significant protection against PDCoV infection.