All animals survived after jugular vein dosing. Tail vein injection of HAdV-5 increased the mortality rate to 42 % (p ≤ 0.01). All deaths occurred within 4 h. Animals dosed through the jugular vein had significantly higher levels of transgene expression in the liver and spleen and significantly more viral genomes in these tissues and kidney and lung within the first 24 h of viral infection compared to those dosed by tail vein injection (p ≤ 0.01). There was no significant difference between the groups thereafter. Samples from animals that died contained even higher levels of viral genomes and serum transaminases were elevated on average by a factor of 4 at the time of death. There was no significant difference between the two dosing methods with respect to changes in hepatic cytochrome P450 expression and activity throughout the study.
These findings suggest that the method of systemic administration should be carefully considered when assessing toxicity data and other parameters at early time points after virus administration in the rat and possibly other animal models.