Most infectious diseases are caused by pathogenic infiltrations from the mucosal tract. Therefore, vaccines delivered to the mucosal tissues can mimic natural infections and provide protection at the first site of infection. Thus, mucosal, especially, oral delivery is becoming the most preferred mode of vaccination. However, oral vaccines have to overcome several barriers such as the extremely low pH of the stomach, the presence of proteolytic enzymes and bile salts as well as low permeability in the intestine. Several formulations based on nanoparticle strategies are currently being explored to prepare stable oral vaccine formulations. This review briefly discusses several molecular mechanisms involved in intestinal immune cell activation and various aspects of oral nanoparticle-based vaccine design that should be considered for improved mucosal and systemic immune responses.

Most pathogens gain access to the human body and initiate systemic infections through mucosal sites. A large number of currently marketed licensed vaccines are parenterally administered; they generate strong systemic immunity but not mucosal immunity. Nasal vaccination is an appealing strategy for the induction of mucosal-specific immunity; however, its development is mostly challenged by several factors, such as inefficient antigen uptake, its rapid mucociliary clearance, size-restricted permeation across epithelial barriers and absence of safe human mucosal adjuvants. Therefore, a safer mucosal-adjuvanting strategy or efficient mucosal delivery platform is much warranted. This review summarizes challenges and the rationale for nasal vaccine development with a special focus on the use of nanoparticles based on polymers and lipids for mucosal vaccine delivery.