Bacterial Spore-Based Delivery System: 20 Years of a Versatile Approach for Innovative Vaccines

Mucosal vaccines offer several advantages over injectable conventional vaccines, such as the induction of adaptive immunity, with secretory IgA production at the entry site of most pathogens, and needle-less vaccinations. Despite their potential, only a few mucosal vaccines are currently used. Developing new effective mucosal vaccines strongly relies on identifying innovative antigens, efficient adjuvants, and delivery systems. Several approaches based on phages, bacteria, or nanoparticles have been proposed to deliver antigens to mucosal surfaces. Bacterial spores have also been considered antigen vehicles, and various antigens have been successfully exposed on their surface. Due to their peculiar structure, spores conjugate the advantages of live microorganisms with synthetic nanoparticles. When mucosally administered, spores expressing antigens have been shown to induce antigen-specific, protective immune responses. This review accounts for recent progress in the formulation of spore-based mucosal vaccines, describing a spore’s structure, specifically the spore surface, and the diverse approaches developed to improve its efficiency as a vehicle for heterologous antigen presentation.