 The purpose of this research is to compare the ability of a new investigational smallpox vaccine called IMVAMUNE to produce a strong immune response against smallpox disease if given as one single, higher dose compared with two lower doses given one month apart. Another purpose of the study is to see how quickly someone might be protected against smallpox. Volunteers will be vaccinia-naïve adults age 18 and older born after 1971 divided into 2 groups. Volunteers in Group A will receive a high dose of vaccine given in 2 shots on day 0 followed by a placebo inactive substance shot on day 28. Group B will receive the standard dose of vaccine and placebo given in 2 shots on day 0 followed by a standard dose shot on Day 28. Study participation will include 10 planned study visits over approximately 7 months. 