Development of a vaccine based on mRNA assembly of PEDV virus-like particle.

Porcine epidemic diarrhea virus (PEDV) represents a highly contagious enteropathogenic coronavirus affecting swine. This virus elicits acute diarrhea in neonatal nursing piglets, with mortality approaching 100%, and, thus, imposes enormous economic burdens on the worldwide pork industry. Therefore, developing safe and effective vaccines remains a top priority for controlling PEDV. Here, we constructed a lipid-nanoparticle (LNP)-encapsulated messenger RNA (mRNA) vaccine. This vaccine encodes the four major structural proteins of PEDV: spike (S), membrane (M), envelope (E), and nucleocapsid (N), which self-assemble into virus-like particle (VLP). Compared with a PEDV S-only mRNA vaccine and a commercial PEDV/transmissible gastroenteritis virus (TGEV) bivalent inactivated vaccine in a mouse model, this VLP mRNA vaccine induced significantly higher levels of IgG, mucosal IgA, and neutralizing antibodies. It also enhanced the lymphocyte proliferation index and expanded the populations of T and B cells. Subsequent evaluations in sows showed that the VLP mRNA vaccine elicited robust PEDV-specific immune responses in vivo. Furthermore, piglets that suckled colostrum from these vaccinated sows gained protection against challenge with a virulent PEDV strain. These protected piglets exhibited lower diarrhea scores, reduced viral shedding, less severe intestinal lesions, and decreased mortality. Collectively, these findings demonstrate that the developed PEDV VLP mRNA platform constitutes a highly promising strategy for preventing PEDV infections.IMPORTANCEPEDV-induced watery diarrhea in neonatal piglets remains a major threat to the global swine industry, while current commercial vaccines are predominantly inactivated formulations or S-only subunit vaccines, whose efficacy and broad-spectrum protection continue to be limited. We, therefore, incorporated the four PEDV structural proteins (S-M-E-N) into a LNP mRNA vaccine that self-assembles into VLPs in vivo. In mice, the mRNA-VLP platform elicited significantly higher systemic IgG, mucosal IgA, and neutralizing antibody titers than an S-only mRNA control or a commercial PEDV/TGEV inactivated vaccine, while expanding both T- and B-cell populations. Maternal immunization of pregnant sows converted these responses into potent systemic immunity that protected suckling piglets against virulent challenge, as evidenced by markedly reduced diarrhea scores, intestinal lesions, viral shedding, and mortality. Collectively, the developed PEDV mRNA-VLP platform offers a highly promising strategy for preventing PEDV infection.