A Self-Amplifying RNA Lipid Nanoparticle (saRNA-LNP) Vaccine Provides Effective Protection Against Porcine Epidemic Diarrhea.

The development of vaccine platforms capable of inducing sustained, potent, and cost-effective immunity remains a major challenge in veterinary vaccinology, particularly for coronaviruses, which are often associated with short-lived vaccine-induced protection. Here, we establish a self-amplifying RNA (saRNA) lipid nanoparticle (LNP) vaccine platform and evaluate its application using porcine epidemic diarrhea virus (PEDV) as a representative coronavirus model. A single vaccination elicited robust specific humoral and cellular immune responses. Vaccinated piglets exhibited significantly higher specific IgG and neutralizing antibody titers of PEDV-S (1:160) at 28 days postvaccination (dpv). Furthermore, elevated levels of serum IFN-γ and IL-4, along with enhanced CD4+ and CD8+ T cells, were observed. Vaccinated pregnant sows exhibited significantly higher PEDV neutralizing antibody titers (~1:224 or 256) in serum and colostrum samples. The saRNA-LNP vaccine conferred both active immune protection against PED in immunized piglets and passive immunity in neonates via colostrum-derived antibodies from vaccinated sows. Notably, the truncated spike protein antigen outperformed the full-length spike protein in terms of immunogenicity, revealing the importance of careful testing in designing this PEDV saRNA vaccine. The saRNA-LNP system represents a dose-sparing, single-dose vaccine platform with the potential to extend protective immunity, enhance maternal antibody responses, and reduce vaccination costs for PEDV and other veterinary coronaviruses.