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

Fausther-Bovendo, Hugues; Kobinger, Gary P

zation is due to high sequence heterogeneity of targeted epitopes such as hexon HVR or fiber knob. 19, 21, 23, 24 However, non-neutralizing but cross-reactive Ab are also generated, especially after repeated Ad injections. 25 These non-neutralizing Abs can also reduce transgene expression, presumably using various Fc receptor dependent (such as antibody dependent cellular cytotoxicity, complement mediated lysis or opsonisation) and independent mechanisms. The impact of non-neutralizing Abs was elegantly illustrated by Pichla-Gollon and colleagues who demonstrated that passive transfer of an Ab able to bind, but not neutralize, could reduce transgene expression as well as immunogenicity of a modified Chad68 vector. 26 The inhibitory effect of cross-reactive but non neutralizing Ab is of particular concern, as these Abs seem to be readily inducible. 25