Design of Mucosal Vaccines Against Swine Enteric Coronaviruses: From Antigen Delivery to Immune Activation.

Swine enteric coronaviruses (SeCoVs) cause acute enteritis and high mortality in neonatal piglets, posing a significant threat to the swine industry. Injectable vaccines often fail to induce effective mucosal immunity, and their efficacy is further compromised by maternally derived antibodies. Oral and intranasal mucosal vaccines offer promising alternatives, enabling localized and durable protection. This review summarizes recent advances in mucosal vaccines against SeCoVs, focusing on antigen delivery platforms and mucosal immune activation. Novel antigen delivery platforms, including nanoparticles (NPs), hydrogels, engineered probiotics, recombinant viral vectors, and eukaryotic expression systems, have improved antigen stability and facilitated transport across the epithelium to mucosal inductive sites. Moreover, targeting strategies that focus on microfold cells (M cells) and dendritic cells (DCs) enhance antigen uptake and presentation. These delivery systems promote mucosal immune activation by inducing secretory IgA (sIgA), maintaining Th1/Th2 balance, and promoting the generation of T and B cells. In addition, the incorporation of adjuvants further strengthens these responses, resulting in more robust and durable protection. By synergistically integrating advanced mucosal vaccine delivery systems with rational adjuvant strategies, this review provides theoretical and practical perspectives for the development of safe, effective, and broadly protective mucosal vaccines targeting SeCoVs infections.