Next-generation mucosal vaccines for respiratory viruses: Immunological correlates, platform design and clinical translation

Influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 continue to cause substantial morbidity and mortality. Currently licensed intramuscular (IM) vaccines effectively reduce severe disease and death but only partially suppress infection and transmission because they induce limited immunity in the respiratory mucosa. This minireview summarizes next-generation mucosal vaccines for respiratory viruses, focusing on the immunological correlates of protection, platform design, and clinical translation. The literature was identified through focused searches of PubMed and Scopus, prioritizing human studies and late-stage preclinical data published between 2000 and 2025. We outline the key mucosal immune correlates required to block viral entry at the airway epithelium, including secretory IgA and tissue-resident memory T cells, and review advances across major vaccine platforms. Current clinical experience with coronavirus disease 2019, influenza, and RSV mucosal vaccines is discussed, along with challenges related to immune measurement, delivery optimization, evaluation of transmission outcomes, and scalable global implementation, including heterologous systemic-mucosal prime-boost strategies. Overall, accumulating evidence positions mucosal vaccination as a promising complement to IM vaccines, with the potential to shift respiratory virus control from disease mitigation to prevention of infection and transmission.