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

Fausther-Bovendo, Hugues; Kobinger, Gary P

Due to the wide distribution of Ad reactive T cells, preexisting Ad immunity might be more widespread than previously thought. Indeed, most studies solely rely on the presence of nAbs against Ad to assess seroprevalence. However in a few studies, both nAbs and cellular response against Ad were assessed and a higher proportion of individuals possessed T cell responses compare with nAbs against Ad. For example, in a study by Calcedo and colleagues, only 28% of tested individuals had neutralizing Ab against HAd5 whereas all of these individuals had Ad specific T cell responses as measured by Enzyme-Linked ImmunoSpot (ELISPOT). 33 Similarly, a higher proportion of individuals had Ad specific T cell responses (64%) compared with neutralizing Ab against HAd5 (55%) in another study. 35 In addition to being widely distributed and cross-reactive, Ad specific T cells were mainly effector memory T cells that could readily be reactivated in vitro 28 and were polyfunctional. 33, 34 This high potency may result from frequent reactivation by infection with different Ad serotypes. 28, 33, 34 Taken together, due to their ability to cross-react with Ad from different sub-groups, their wide-distribution in the human population and their high potency, the impact of Ad specific T cells cannot be overlooked when developing future Ad vectors.