Mucosal immunity and vaccine development

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Not quantified — no pooled effect sizes reported; findings are narrative and mechanistic

• Primary Outcome: Characterisation of mucosal immune mechanisms and comparative evaluation of mucosal versus parenteral vaccine delivery platforms for induction of local mucosal immunity (secretory IgA, tissue-resident memory T and B cells) and systemic immune responses

• Nnt Or Sensitivity: Not calculable from this review — no clinical trial-level data are pooled; qualitative conclusion that mucosal vaccines can simultaneously elicit local mucosal and systemic immune responses, potentially blocking pathogen entry more effectively than intramuscular vaccines

• Confidence Interval: Not reported — no meta-analytic synthesis performed

Clinical Application

Mucosal vaccine delivery (intranasal, oral, sublingual) is feasible in high-income healthcare settings and potentially more scalable in low-resource settings due to reduced cold-chain requirements and elimination of needle/syringe infrastructure. However, regulatory pathways for novel mucosal adjuvants and delivery systems remain complex. Clinical translation of many platforms discussed remains at preclinical or early-phase trial stages. In Australia, mucosal vaccines are of direct relevance given the TGA's regulatory oversight of novel vaccine platforms and the ATAGI framework for vaccine recommendations. The intranasal live-attenuated influenza vaccine (Fluenz Tetra) has TGA registration and is available for eligible children. No mucosal COVID-19 vaccines are currently TGA-approved or PBS-listed. The RACGP supports evidence-based vaccination strategies, and this review's conceptual framework may inform future ATAGI position statements on next-generation mucosal vaccines. Australia's geographic isolation and biosecurity priorities make mucosal vaccines for pandemic preparedness particularly strategically relevant. The National Immunisation Program (NIP) could benefit from mucosal vaccine options that improve coverage in needle-phobic or hard-to-reach populations. Broadly applicable to all populations at risk of mucosal pathogen exposure, including those at risk for respiratory infections (influenza, SARS-CoV-2, RSV), gastrointestinal infections (rotavirus, norovirus, Helicobacter pylori), and sexually transmitted infections (HIV, HPV). Particularly relevant for immunocompromised individuals, elderly populations, and settings where needle-based vaccination is logistically challenging.

Abstract

The mucosal system, which includes the respiratory, gastrointestinal, and urogenital tracts, serves as a primary entry point for pathogens, with a unique immune microenvironment and specialized defense mechanisms. In recent years, especially following the onset of the COVID-19 pandemic, there has been increasing recognition of the importance of mucosal immunity, motivated by an enhanced comprehension of its fundamental mechanisms. Currently, strategies based on mucosal delivery systems to administer antigens and induce strong mucosal protective immunity have become a key focus in the development of mucosal vaccines. Compared with conventional intramuscular delivery, mucosal vaccination can simultaneously elicit a robust local mucosal response, effectively block pathogen entry into the local mucosa, and generate systemic immune responses to prevent symptomatic infections and severe disease. In addition, mucosal delivery offers advantages such as ease of administration and low invasiveness, making it a more widely acceptable approach to vaccination. In the present study, we conducted a systematic review of the mechanisms of mucosal immunity, the technological platforms for mucosal vaccines, and proposed a perspective on the challenges and future directions for the development of next-generation mucosal vaccines, with the goal of enhancing public knowledge and awareness regarding mucosal immunity and its possible effects on global health.

References

1. 1.Hong, W., Alu, A., Zhang, Z., Zhang, Y., He, X., Xu, L., Li, M., He, W., & Wang, J. (2026). Mucosal immunity and vaccine development. Signal Transduction and Targeted Therapy. https://doi.org/10.1016/j.cell.2025.07.022