An adenovirus 5 vector encoding for mouse
interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal
cowpox (Brighton strain) and
vaccinia (WR strain) virus respiratory and systemic
infections in mice. Two routes of mDEF201 administration were used, nasal sinus (5-µl) and pulmonary (50-µl), to compare differences in efficacy, since the preferred treatment of humans would be in a relatively small volume delivered intranasally. Lower
respiratory infections (LRI),
upper respiratory infections (URI), and systemic
infections were induced by 50-µl intranasal, 10-µl intranasal, and 100-µl intraperitoneal virus challenges, respectively. mDEF201 treatments were given prophylactically either 24 h (short term) or 56d (long-term) prior to virus challenge. Single nasal sinus treatments of 10(6) and 10(7) PFU/mouse of mDEF201 protected all mice from
vaccinia-induced LRI mortality (comparable to published studies with pulmonary delivered mDEF201). Systemic
vaccinia infections responded significantly better to nasal sinus delivered mDEF201 than to pulmonary treatments.
Cowpox LRI
infections responded to 10(7) mDEF201 treatments, but
a 10(6) dose was only weakly protective.
Cowpox URI
infections were equally treatable by nasal sinus and pulmonary delivered mDEF201
at 10(7) PFU/mouse. Dose-responsive prophylaxis with mDEF201, given one time only 56 d prior to initiating a vaccinia virus LRI
infection, was 100% protective from 10(5) to 10(7) PFU/mouse. Improvements in lung
hemorrhage score and lung weight were evident, as were decreases in liver, lung, and spleen virus titers. Thus, mDEF201 was able to treat different
vaccinia and cowpox virus
infections using both nasal sinus and pulmonary treatment regimens, supporting its development for humans.