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

Fausther-Bovendo, Hugues; Kobinger, Gary P

In addition to nAbs, Ad specific T cells also decrease vector efficacy. Despite the fact that passive transfer of either serum or T cells from HAd5 immune mice can significantly decrease cellular and humoral response against the insert after HAd5 immunization, 16 less attention has been given to the role of Ad specific T cells in pre-existing Ad vector immunity. Although, passive transfer of nAbs induced a greater inhibition of HAd5 induced immune response, they did not inhibit Ad immune stimulation to levels observed in Ad5 pre-immune mice, 16 pointing at the contribution of Ad specific T cells in dampening HAd immunogenicity in pre-immune subjects. Depletion of T cells in Ad immune animals would provide a more accurate evaluation of T cell contribution as both circulating and tissue-resident T cells will be taken into account.