Self-Assembled PEDV Virus-Like Particle Nanovaccines Elicit Potent Neutralizing Antibodies and Confer Full Protection in Piglets.

Porcine epidemic diarrhea virus (PEDV) remains a major threat to the global swine industry, with current inactivated vaccines offering limited cross-protection due to imperfect antigen design and weak immune activation. Here, we engineered a full-structural-protein virus-like particle (VLP) co-assembled with PEDV S, M, N, and E proteins into uniform nanoscale particles, further formulated with a dual-adjuvant system of AS03 and CpG ODN. The VLP + AS03 + CpG nanovaccine elicited 10-12-fold higher PEDV-specific IgG than unadjuvanted VLPs, outperformed a commercial inactivated vaccine in mice, and induced a balanced Th1/Th2 response with elevated IL-4, IFN-γ, IL-10, and IL-17A. In piglets, the nanovaccine conferred robust protection against PEDV challenge, reducing jejunal viral load by 79% and preserving intestinal mucosal barrier integrity. This work presents a promising PEDV vaccine candidate and a broadly applicable strategy for coronavirus VLP vaccine design.