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Nasal and Pulmonary Immunology: Choosing the Optimal Vaccine Delivery Route

Patton JS, Scherließ R, MacLoughlan R, Hickey AJ.

Respiratory Drug Delivery 2025. Volume 1, 2025: 27-38.

Abstract:

The practice of delivering vaccines onto the surfaces of our bodies like our skin and respiratory system is many centuries old. It has not been appreciated that this manner of vaccination has impressive advantages over injecting vaccines into the body and by-passing the entry points (mucosa and skin) where so many powerful immunological weapons against infection reside. The last 80–90 years of immunological research into vaccines have now revealed how mucosal immunization and protection against infection work. Now many companies are studying nasal spray and inhaled respiratory vaccines (as well as oral and epidermal). A bias arose that for respiratory, it might be best to deliver the vaccine exclusively into the nose and keep it out of the lungs for safety reasons. And that nasal immunization mechanisms were connected to pulmonary processes and full respiratory protection could be affected with local delivery only to one region of the respiratory system i.e., the nose. A culmination of research on the mechanisms of respiratory mucosal immunology now reveal that respiratory defense against infections is comprised of many independent sub-regions each served by their own lymph nodes and capable of inducing long lasting immune protection and that the best vaccine could be the one that ‘paints all the rooms of the house’. An aerosol could be the painter. An inhaled vaccine could be optimized to hit all the mucosal surfaces in one or two inspirations – the perfect vaccine.