Despite the declaration of smallpox eradication in 1980, the existence of 
variola stockpiles and the threat of bioterrorism demand that immunity to 
smallpox through vaccination be maintained. Although the currently available 
vaccine was used for the most successful medical intervention ever accomplished, 
it also is associated with side effects that are difficult to accept in a 
vaccine for a disease that has not been present for >25 years. Herein, we review 
alternative approaches to maintaining immunity to smallpox through vaccination 
with attenuated poxviruses, and we suggest modified vaccinia Ankara (MVA) as a 
leading candidate for an alternative smallpox vaccine.