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Mucosal vaccines — fortifying the frontiers

Nature Reviews Immunology volume 22, pages 236–250 (2022)Cite this article

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A Publisher Correction to this article was published on 03 August 2021

This article has been updated

Abstract

Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection. In principle, the induction of adaptive immunity at mucosal sites, involving secretory antibody responses and tissue-resident T cells, has the capacity to prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms. Although numerous effective mucosal vaccines are in use, the major advances seen with injectable vaccines (including adjuvanted subunit antigens, RNA and DNA vaccines) have not yet been translated into licensed mucosal vaccines, which currently comprise solely live attenuated and inactivated whole-cell preparations. The identification of safe and effective mucosal adjuvants allied to innovative antigen discovery and delivery strategies is key to advancing mucosal vaccines. Significant progress has been made in resolving the mechanisms that regulate innate and adaptive mucosal immunity and in understanding the crosstalk between mucosal sites, and this provides valuable pointers to inform mucosal adjuvant design. In particular, increased knowledge on mucosal antigen-presenting cells, innate lymphoid cell populations and resident memory cells at mucosal sites highlights attractive targets for vaccine design. Exploiting these insights will allow new vaccine technologies to be leveraged to facilitate rational mucosal vaccine design for pathogens including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for cancer.

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Fig. 1: Burden of mucosal diseases with unmet vaccine needs.
Fig. 2: Licensed mucosal vaccines.
Fig. 3: Vaccine uptake at mucosal sites.

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Acknowledgements

The authors thank N. Muñoz-Wolf for critical reading of the manuscript. The mucosal vaccine research from the Lavelle laboratory has been funded by Science Foundation Ireland (SFI) (Grant numbers 12/IA/1421, 19/FFP/6484, SFI/12/RC/2278_2, 20/SPP/3685), the Irish Research Council and the European Union FP7 programme (FP7-SME-2012-1).

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  1. Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland

    Ed C. Lavelle & Ross W. Ward

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Glossary

Chitosan

A cationic polymer derived from chitin with mucosal adjuvant properties. In addition to its mucoadhesive attributes, chitosan promotes adaptive immunity through activation of the cGAS–STING and NLRP3 inflammasome pathways.

Enchained growth

A process where high-affinity IgA specific for surface antigens cross-links bacteria, preventing daughter cell separation after division and contributing to clearance of mucosal pathogens.

Microfold (M) cells

Specialized antigen sampling epithelial cells generally found in the follicle-associated epithelium overlying organized mucosal lymphoid tissue.

Polymersomes

Hollow vesicles generally comprising block copolymers that can incorporate vaccine antigens and adjuvants in the aqueous phase.

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Lavelle, E.C., Ward, R.W. Mucosal vaccines — fortifying the frontiers. Nat Rev Immunol 22, 236–250 (2022). https://doi.org/10.1038/s41577-021-00583-2

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