Mucosal vaccine development for respiratory viral infections

Mucosal vaccines have risen to prominence in the corona virus disease 2019 (COVID-19) pandemic due to their ability to elicit both local antibody and tissue-resident T cell responses, affording a dual-layered defense against infection and transmission at respiratory entry sites. While intramuscular vaccines predominantly focus on systemic immunity, mucosal vaccines offer a more nuanced, site-specific approach. However, the field faces a dearth of mucosal vaccine options for respiratory diseases, starkly contrasting to the extensive array of well-characterized injectable vaccines. The unique features of mucosal surfaces necessitate specialized adjuvants and delivery systems, adding complexity to adapting injectable vaccine technologies for mucosal applications. Here, we review the recent insights into the specificities of respiratory mucosal immunology that provide a foundation for future innovations besides the emerging vaccine platforms, newly discovered adjuvants, and vaccine delivery systems, which may open promising avenues for developing mucosal vaccines targeting respiratory pathogens.