Advances of inhaled vaccine research

Respiratory infections, as common diseases, along with other respiratory system diseases such as asthma, rare diseases including cystic fibrosis, chronic obstructive pulmonary disease, and lung cancer, can be prevented using vaccines. Taking respiratory infections as an example, vaccines are mostly administered via intramuscular injection, inducing the production of serum IgG, thereby neutralizing viral infectivity and alleviating COVID-19 symptoms. However, due to the lack of secretory IgA and IgG in muscle tissues, intramuscular vaccines cannot quickly provide protection to the respiratory tract. To overcome the shortcomings of intramuscular injection, some vaccine candidates for nasal or nebulized inhalation are under development or have been approved. Clinical studies show that inhaled vaccines can induce antibody responses similar to those of intramuscular vaccines at much lower doses. Inhaled vaccines can simultaneously induce humoral, cellular, and mucosal immunity, providing triple protection. With the application of new vaccines (e.g. mRNA vaccines and DNA vaccines) in inhalable formulations for COVID-19, inhaled vaccines have been proven to have broad application prospects in the prevention of lung diseases. Given this background and the known abundance of immune cells in the lungs, increasing research efforts are devoted to developing single-dose inhalable nano dry powder vaccines. This article discusses the roles and advantages of inhaled vaccines in mucosal immunity, their potentials for treating different diseases, and prospects for the future development of inhaled vaccines based on nanotechnology.