Pre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what's important?

Fausther-Bovendo, Hugues; Kobinger, Gary P

In pre-clinical studies, alternating the immunization route has bypassed pre-existing Ad immunity. Immunization through the airway holds promise and may turn out to be a delivery method of choice for inducing potent and long lasting protective immune responses from an Ad vector. While the airway may be a viable solution to bypass pre-existing immunity, several remaining questions will need to be addressed. Despite the relatively rapid turnover of resident immune cells and IgA in the lungs, the effect of immune stimulation following natural Ad exposure or vaccination will be critical to determine whether the same or other Ad vectors can be re-administer in the airway, at what frequency, and according to what regimen (single dose vs. prime-boost). This knowledge should ultimately inform on the number of independent vaccines one antigenic Ad backbone could be used for. Ultimately, this will have to be determined in clinical studies.