Harnessing mucosal immunity for protective vaccines

Mucosal surfaces are primary entry sites for many infectious pathogens, yet parenteral vaccination alone often fails to elicit effective mucosal immunity. Mucosally delivered vaccines offer a promising strategy for reinforcing frontline defences and inducing localized, pathogen-specific immune responses. Recent studies indicate that mucosal vaccines elicit tissue-resident memory T and B cells, along with robust local antibody secretion, to prevent infection and transmission. However, achieving sterilizing immunity at mucosal sites proves challenging owing to the complex immune environments consisting of epithelial barriers, varying mucus composition, pH differences and hormonal influences. In this Review, we outline how specialized immune-inductive and effector mechanisms across distinct mucosal compartments contribute to protective immunity and discuss emerging strategies to harness multilayered mucosal immunity to develop safe, effective vaccines that elicit durable protection.