Previous studies in mice with a related DEF201 virus expressing mouse IFN-a (mDEF201) have shown the utility of adenovirusbased system to counter viral infections [20, 32, 33] . More recently, in a different hamster model of viral hemorrhagic fever, several of us reported on efficacy of DEF201 in mitigating YFV infection and disease [19] . YFV infection appears to be more sensitive to the effects of DEF201, as a lower dose was able to provide complete protection. Taken together with the results of the present study, the experimental animal data support the broad use of DEF201 for extended pre-exposure and early post-exposure prophylaxis applications. Further investigations using advanced arenavirus models based on challenge of nonhuman primates with pathogenic arenaviruses [17] are needed to better evaluate the potential of DEF201 to prevent severe disease in humans. Nonhuman primate models should allow the full spectrum of cIFN-a activity not possible in hamsters or guinea pigs.