Lethal Toxicity,Severe Endothelial Injury,and a Threshold Effect with High Doses of an Adenoviral Vector in Baboons

The effects of intravenous administration of a first-generation adenoviral vector expressing β-galactosidase were compared in two baboons receiving a high dose or lower dose of vector, 1.2 × 10¹³ or 1.2 × 10¹² particles/kg, respectively. The high-dose baboon developed acute symptoms, decreased platelet counts, and increased liver enzymes, and became moribund at 48 hr after injection, while the lower-dose baboon developed no symptoms. Expression of the β-galactosidase transgene was prominent in liver, spleen, and endothelium of the arterial vasculature in the high-dose baboon, but was much more limited and spared the endothelium in the lower-dose baboon. Injury to the vascular endothelium was the most prominent abnormality in the high-dose baboon. Extensive histological studies provide a detailed picture of the pathology associated with a lethal dose of first-generation adenoviral vector in a primate.