N-terminal Domain of the Spike Protein of Porcine Epidemic Diarrhea Virus as a New Candidate Molecule for a Mucosal Vaccine

Kim, Sae-Hae; Cho, Byeol-Hee; Lee, Kyung-Yeol; Jang, Yong-Suk

Porcine epidemic diarrhea virus (PEDV), a causative agent of PED, was first described as a devastating enteric disease of pigs in the United Kingdom in 1971 (1) . PEDV is a member of the Alphacoronavirus genus that has a single-stranded positive-sense RNA genome (2) . PEDV infection induces diarrhea, causing high mortality in suckling piglets and weight loss in older hogs, which have led to significant economic losses in the swine industry (3) . The PEDV genome consists of seven open reading frames encoding four structural proteins, the spike (S) glycoprotein, membrane protein, envelope protein, and nucleocapsid protein (4) . Among the structural proteins, the S glycoprotein consists of the S1 and S2 domains. The C-terminal domain (CTD) of the S1 protein has been considered a major target Ag inducing neutralizing Ab production, because it interacts with aminopeptidase N (APN), a functional receptor involved in PEDV infection, on the host cell membrane (5) . Based on the observation that PEDV infection occurs mainly in epithelial cells of the small intestine via the fecal-oral route, and gross lesions are detected in the gastrointestinal tract of PEDV-infected animals, the establishment of mucosal immunity is required to induce protective immunity against PEDV infection (6, 7) . However, a mucosal PEDV vaccine is not available, and inducing mucosal immunity is difficult with current PEDV vaccine materials, which are administered intramuscularly, because the gut mucosa has a unique immune system, into which Ags enter only from the intestinal lumen due to the lack of afferent lymphatic vessels in mucosal immune-inductive site, compared with that of the systemic immune system. Interestingly, recent reports suggest that the N-terminal domain (NTD) of S protein also interacts with 5-N-acetylneuraminic acid, a possible sugar co-receptor, expressed on epithelial cells and aids in PEDV infection in the host (8) . Consequently, use of the NTD as a mucosal vaccine material is a plausible vaccination strategy to protect against PEDV infection.