Engineering next-generation nanovaccines for maternal immunization and piglet protection against porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) remains a major threat to the global swine industry, causing severe disease with high morbidity and mortality in neonatal piglets. Current vaccine strategies are challenged by the need for rapid, local protection at the intestinal mucosa in newborn piglets, and emerging PEDV variants can partially evade vaccine immunity. Nanoplatforms can help address these challenges. Across recent PEDV nanovaccine studies, a consistent theme emerges in that vaccine platform architecture and immunization route are not only delivery parameters but also the primary determinants of neutralizing activity, mucosal IgA induction, and lactogenic immunity transfer. Here in this critical review, we synthesize important design perspectives from the PEDV nanoparticle vaccine literature spanning self-assembling protein scaffolds such as ferritin and mi3, bacteriophage and virus-like particles including AP205 and HBcAg, polymeric carriers such as PLGA, chitosan, and alginate-chitosan microcapsules, and inorganic particles including silica and layered double hydroxide. All PEDV vaccine design considerations are organized into three interlocking layers including antigen choice and display, adjuvant-carrier integration, and maternal-mucosal vaccination strategy. Concurrently, mechanistic patterns are observed across models. For instance, multivalent display strengthens protective breadth, and mucoadhesive or M-cell-targeted approaches improve antigen retention and epithelial transport. Practical vaccine design principles are derived throughout this review to support translation of PEDV nanoparticle vaccines into maternal immunization strategies focused on protecting piglets against PEDV variants.