Host immune responses and toxicology. Neutralizing antibodies (NABs) directed at the AAV capsid trend upward with higher dosing in both intraocular fluid and serum. A T cell response (detected by ELISPOT assay) directed at GFP developed in two animals exposed to the highest dose of either AAV2 or AAV8. Histopathological analyses showed retinal infiltrates (observed in H&E-stained sections) in the retinas of those animals as well as in the retina of one animal that had experienced a retinal hemorrhage during the injection procedure (“hemorrhage”). Analyses of NAB responses compared baseline levels of anterior chamber (AC) fluid and serum with samples at the termination of the experiment. The T cell–mediated immune response to GFP compared baseline measurements (“Pre-ex. capsid T”) with measurements taken 2 weeks after injection of AAV (“Capsid T 2w”) and at the termination of the study at 20 weeks (“GFP T 20w”). There was no correlation between expression of GFP in the optic nerve or optic chiasm and an immune response. Animals are identified by number. L, left eye; R, right eye; GFP, green fluorescent protein.
