Engineering mucosal immunity: Advanced vaccine platforms against respiratory pathogens

Respiratory tract infections present a major global health challenge, necessitating vaccines that induce potent mucosal immunity to prevent infection and transmission. This review explores the rational design of next-generation mucosal vaccines through technological innovations in antigen engineering, adjuvant platforms, and delivery systems. We detail structure-based antigen stabilization and multivalent display strategies to enhance immunogenicity and cross-protection. The synergistic use of delivery vehicles and immunostimulatory adjuvants, including TLR and STING agonists, is highlighted for their ability to potentiate robust immune responses while overcoming mucosal tolerance. Additionally, we examine needle-free administration, CRISPR-based antiviral approaches, and tailored formulations for high-risk populations. Despite promising advances, clinical translation remains hindered by biological barriers, safety issues, and manufacturing constraints. This review offers a comprehensive perspective on engineered mucosal immunization and its potential to combat respiratory pathogens.