Protein nanocages: A new frontier in mucosal vaccine delivery and immune activation

Mucosal infectious diseases represent a significant global health burden, impacting millions of people worldwide through pathogens that invade the respiratory, gastrointestinal, and urogenital tracts. Mucosal vaccines provide a promising strategy to combat these diseases by preventing pathogens from entering through the portals as well as within the systemic response compartment. However, challenges such as antigen instability, inefficient delivery, suboptimal immune activation, and the complex biology of mucosal barriers hinder their development. These limitations require integrating specialized adjuvants and delivery systems. Protein nanocages, self-assembling nanoscale structures that can be engineered, may provide an innovative solution for co-delivering antigens and adjuvants. With their remarkable stability, biocompatibility, and design versatility, protein nanocages can potentially overcome existing challenges in mucosal vaccine delivery and enhance protective immune responses. This review highlights the potential of protein nanocages to revolutionize mucosal vaccine development by addressing these challenges.