Repeated administration of adenoviral vectors in lungs of human CD4 transgenic mice treated with a nondepleting CD4 antibody

The central role of CD4(+) T cells in regulation of adenovirus vector-media ted immune responses has been documented previously in murine models. We an alyzed the effects of a nondepleting mAb to human CD4 (CD? mAb; Clenolixima b) on immune functions following intratracheal administration of adenoviral vectors in murine CD4-deficient mice (muCD4KO) expressing a human CD4 tran sgene (HuCD4 mice). Treatment of HuCD4 mice with Clenoliximab inhibited bot h cell-mediated and humoral immune responses to adenoviral Ags, Chronic tre atment of HuCD4 mice with Clenoliximab permitted successful readministratio n of adenoviral vectors at least four times. The ability to readminister th ese vectors is associated with merited suppression of neutralizing Ab respo nses to viral capsid proteins. Clenoliximab also inhibited CTL and prolonge d expression of the transgene, T or B cell responses to adenovirus did not emerge after the effects of a short course of Clenoliximab diminished. Thes e data illustrate the potential utility of a nondepleting CD4 Ab in facilit ating gene therapy using adenoviral vectors.