A user’s guide to designing efficient and safe mucosal vaccines: Challenges & potentials

Abstract

Mucosal immunization represents a promising approach to protect against pathogens that enter through mucosal surfaces. This review provides a practical overview of the mucosal immune system’s main features and explores the benefits of mucosal vaccination, including its capacity to induce both local and systemic immune responses. Key challenges—such as mechanical barriers, the tolerogenic nature of mucosal immunity and variability due to environmental influences—are examined in detail. Strategies to overcome mucosal tolerance, improve antigen uptake and enhance immunogenicity are discussed, alongside recent advances that combine multiple mucosal routes or explore less conventional pathways. The review also outlines practical considerations for optimizing vaccine delivery and evaluating immune responses, offering a user-oriented guide to the current landscape and future directions in mucosal vaccine development.