Overcoming Antigenic Drift in PEDV: Broadly Protective Antigen Design and sIgA-Driven Lactogenic Immunity.

Porcine epidemic diarrhea virus (PEDV) remains one of the most critical enteric coronaviruses affecting the global swine industry. PEDV causes severe diarrhea, dehydration, and high mortality in neonatal piglets. Despite the widespread use of commercial vaccines, persistent PEDV outbreaks worldwide indicate that current vaccination strategies provide suboptimal protection. Increasing evidence suggests that the limited effectiveness of current control strategies is primarily attributable to two interrelated factors: continuous antigenic variation among circulating PEDV strains and inadequate induction of maternal mucosal immunity. Unlike systemic viral infections, effective protection against PEDV in neonatal piglets predominantly depends on lactational immunity mediated by the gut-mammary gland-secretory IgA (sIgA) axis. However, most currently available vaccines predominantly induce systemic IgG responses and fail to effectively stimulate intestinal immune imprinting or sustain sIgA secretion in colostrum and milk. In this review, we summarize the mechanisms underlying PEDV evolution and maternal mucosal immunity, with particular emphasis on the gut-mammary gland-sIgA axis. We further discuss the recent advances in and limitations of current vaccine platforms and propose an integrated framework for broadly protective PEDV vaccines based on structural antigen optimization, mucosal-targeted immunization, and sIgA-oriented evaluation systems. This framework may provide new insights into the rational design of more effective maternal vaccines against PEDV and other enteric coronaviruses affecting pigs.