##1. Critical Vulnerability of Neonatal Piglets: PEDV G2c Variant and Placental Barrier Limitations Among porcine epidemic diarrhea virus (PEDV) strains, the G2c genotype variant is a highly virulent pathogen that causes substantial economic losses to swine farms worldwide. Neonatal piglets, due to their epitheliochorial placental structure, receive no antibodies from the dam via the placenta and are therefore agammaglobulinemic at birth. Consequently, PEDV infection leads to dehydration and intestinal barrier disruption, with mortality approaching 100%. Commercial inactivated vaccines have failed to adequately boost maternal mucosal immunity and neutralizing antibody titers in colostrum, leaving this critical gap unaddressed.

##2. Application of Structural Vaccinology: Pre-fusion Stabilization via S-2P Proline Substitutions The research team genetically engineered the PEDV spike (S) protein to retain its pre-fusion conformation, the state prior to membrane fusion with host cells. By introducing silent substitutions that replace residues I1076 and L1077 with proline (I1076P/L1077P), structural flexibility was locked. The resulting stabilized S-2P mRNA presents the key neutralizing epitopes in their native configuration, eliciting markedly higher IgG and immunoglobulin A (IgA) titers compared with a wild‑type (S‑WT) vector.

##3. Maternal Immunity and Passive Transfer: Colostral Protection of the Intestinal Barrier and Microbiota Vaccination of pregnant sows with the S-2P LNP‑mRNA vaccine resulted in extremely high concentrations of neutralizing antibodies in colostrum secreted immediately after farrowing. Neonatal piglets that ingested this colostrum developed a robust IgA barrier on the intestinal mucosa, achieving 100% survival under lethal PEDV G2c challenge without significant barrier damage or gut microbiota dysbiosis.

##4. Establishing a Veterinary mRNA‑LNP Platform and a Bridge for Human Pandemic Preparedness The significance of this work lies in its definitive demonstration of the efficacy and safety of an mRNA‑LNP vaccine targeting an enteric coronavirus in a large‑animal model. By showing that maternal passive immunity can control mucosal infections that are notoriously difficult to protect against, the study establishes a technical standard for rapid adaptation of the mRNA platform to a wide range of livestock diseases. Beyond veterinary impact, the molecular design serves as a critical structural reference for human coronaviruses with similar transmission mechanisms and for next‑generation mucosal vaccine pipelines.