Smallpox vaccines based on replicating vaccinia virus are known to elicit rare 
yet serious adverse events, particularly in human populations with immune 
deficiency, atopic dermatitis and at the extremes of age. A vaccine that induces 
protective immune responses equivalent to first-generation smallpox vaccines 
while reducing the risk for severe adverse events is critical for a national 
stockpile of smallpox vaccines. Modified vaccinia Ankara (MVA) has been proposed 
as an immediate solution for vaccination of high-risk individuals. Bavarian 
Nordic's vaccine MVA-BN (IMVAMUNE) is a MVA strain that is replication 
incompetent in mammalian cell lines. IMVAMUNE has been administered to more than 
1900 human subjects to date, including high-risk populations (e.g., people 
diagnosed with atopic dermatitis or infected with HIV) in which standard 
replicating vaccines are contraindicated. We review the Phase I clinical trial 
safety profile and immune responses and compare them with other smallpox 
vaccines, including ACAM2000 and Dryvax.