Overcoming gastrointestinal mucosal barriers: Mechanistic innovations and technical advances in mucosal targeting strategies for animal oral vaccines.

Infectious diseases caused by pathogenic microorganisms (such as Escherichia coli, Avian influenza virus (AIV), Rotavirus, etc.) that primarily invade through mucosal surfaces like the digestive tract and respiratory tract not only severely restrict the development of the livestock and poultry breeding industry, resulting in huge economic losses, but also threaten public health security due to the risk of cross-species transmission. Oral vaccines, by simulating natural infection routes to activate the mucosal immune system, have advantages such as ease of administration, wide applicability, and avoidance of injection stress, thus becoming an important means to prevent and control mucosal infectious diseases. However, due to the acidic environment of the gastrointestinal tract, degradation by digestive enzymes, and obstruction by mucosal barriers, the stability and immunogenicity of antigens are significantly reduced, which greatly limits the application of oral vaccines. Mucosal targeting strategy is the core technology to break through the above bottlenecks. Through antigen protection and sustained release, precise targeting of immune cells, and carrier adjuvant effect, it can efficiently activate synergistic responses between mucosal immunity (such as secretory immunoglobulin A (SIgA) production) and systemic immunity. This article systematically reviews the technological advances in mucosal targeting strategies for oral vaccines, including the dynamic process of vaccines in vivo, the biological barriers to be overcome, and specific targeting techniques for immune cells such as M cells and dendritic cells. Meanwhile, drawing on cutting-edge applications of drug targeting technology and artificial intelligence in antigen design, it provides theoretical references and research ideas for the construction of safe and efficient mucosal-targeted oral vaccines for animals.