Mucoadhesive Vaccine Delivery Systems for the Oral Mucosa

Vaccine technology has evolved continuously since its beginning, and mucosal vaccination, including intranasal, sublingual, and oral administrations, has recently gained great scientific interest. The oral mucosa represents a promising minimally invasive route for antigen delivery, mainly at sublingual and buccal mucosal sites, and it is easily accessible, immunologically rich, and able to promote an effective systemic and local immune response. The aim of this review is to provide an updated overview on the technologies for oral mucosal vaccination, with emphasis on mucoadhesive biomaterial-based delivery systems. Polymeric-based nanoparticles, multilayer films and wafers, liposomes, microneedles, and thermoresponsive gels are the most investigated strategies to deliver antigens locally, showing mucoadhesive properties, controlled release of the antigen, and the ability to enhance immunological responses. These formulations have achieved adequate properties in terms of vaccine stability, are minimally invasive, and are easy to produce and manage. To date, oral mucosa vaccine delivery systems represent a promising and open field of research. Future directions should focus on the role of these systems to induce sustained innate and adaptive immune responses, by integrating the recent advances achieved in mucoadhesion with those related to vaccine technology. Being painless, easy to administer, highly stable, safe, and effective, the antigen delivery systems via the oral mucosa may represent a useful and promising strategy for fast mass vaccination, especially during pandemic outbreaks.