Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE®

This is a Phase II, randomized, open-label immunogenicity and safety study of different immunization schedules and delivery systems (syringe and needle vs. the Stratis™) in healthy, vaccinia-naïve adults 18 years to 40 years of age, inclusive. Approximately 352 subjects will be enrolled and randomized to one of four study arms. Study Arm A (N=88) will receive a two dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) via the SC route using a syringe and needle on Day 1 and 29. Study Arm B (N=88) will receive a two dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) via the SC route using a syringe and needle on Day 1 and 15. Study Arm C (N=88) will receive a two dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL) via the SC route using a syringe and needle on Day 1 and 22. Study Arm D (N=88) will receive a two dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL) via the SC route using the Stratis™ on Day 1 and 29. Immunogenicity assessments will be performed using ELISA and PRNT. Safety assessments will be done via solicited injection site and systemic reactions. Unsolicited AEs will be collected until 28 days post last injection and SAEs for the duration of the subjects' study participation. Safety laboratory assessments will be performed at baseline and 14 days after each vaccination. Primary outcome measures: For each subject, the peak PRNT will be defined as the highest titer among all available measurements post second vaccination; Occurrence of solicited local injection site reactions in subjects receiving vaccine via the Stratis™ compared to syringe and needle administration as collected on the memory aid and by in clinic assessment. Parent protocol to sub-study 13-0027.