Nanotechnology of inhalable vaccines for enhancing mucosal immunity

Vaccines are the cornerstone of world health. The majority of vaccines are formulated as injectable products, facing the drawbacks of cold chain transportation, needle-stick injuries, and primary systemic immunity. Inhalable vaccines exhibited unique advantages due to their small dose, easy to use, quick effect, and simultaneous induction of mucosal and systemic responses. Facing global pandemics, especially the coronavirus disease 2019 (COVID-19), a majority of inhalable vaccines are in preclinical or clinical trials. A better understanding of advanced delivery technologies of inhalable vaccines may provide new scientific insights for developing inhalable vaccines. In this review article, detailed immune mechanisms involving mucosal, cellular, and humoral immunity were described. The preparation methods of inhalable vaccines were then introduced. Advanced nanotechnologies of inhalable vaccines containing inhalable nucleic acid vaccines, inhalable adenovirus vector vaccines, novel adjuvant-assisted inhalable vaccines, and biomaterials for inhalable vaccine delivery were emphatically discussed. Meanwhile, the latest clinical progress in inhalable vaccines for COVID-19 and tuberculosis was discussed.