Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE®

Inclusion Criteria: 1. 18 to 40 years of age, inclusive. 2. Read, signed, and dated informed consent document. 3. Available for follow-up for the planned duration of the study (six months after last immunization). 4. Acceptable medical history by screening evaluation and limited physical assessment. 5. If the subject is female and of childbearing potential, negative serum or urine pregnancy test at screening and within 24 hours prior to vaccination. 6. If the subject is female and of childbearing potential\*, she agrees to practice abstinence\*\* or use acceptable contraception\*\*\* through 56 days after the last vaccination in order to avoid pregnancy: \* a woman is considered of childbearing potential unless post-menopausal (\>/= 1 year without menses) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy) \*\*No sexual intercourse with men (vaginal penetration by a penis, coitus) \*\*\*Acceptable contraception methods are restricted to effective devices (IUDs, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, condoms with spermicidal agents, monogamous relationship with a vasectomized partner who has been vasectomized for 6 months or more prior to study entry, or successful Essure placement with documented confirmation test at least 3 months after the procedure, and any other FDA-approved contraceptive method 7. Negative test for HIV. 8. Alanine Aminotransferase (ALT) \<1.25 times the central lab upper limit of normal. 9. Negative hepatitis B surface antigen and negative antibody to hepatitis C virus. 10. Negative urine glucose and negative or trace urine protein by dipstick or urinalysis. 11. Adequate renal function (defined as a serum creatinine not exceeding the central lab's upper limit of normal). 12. Electrocardiogram (ECG) with no clinically significant abnormalities\* \* e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrhythmia, or two PVC's in a row, or ST elevation consistent with ischemia) 13. Acceptable hematology parameters: * Hemoglobin (Hgb) equal or above the lower limit of central lab normal (sex-specific); * White Blood Cell (WBC) \> 3,800 and \< 10,900/mm\^3; * Platelets \>/=120,000/mm\^3 14. Body mass index \>/=18.5-\< 35. 15. Be able to understand and comply with planned study procedures. Exclusion Criteria: 1. History of immunodeficiency. 2. Typical vaccinia scar. 3. Known or suspected history of smallpox vaccination including MVA alone or as a vector, as well as other investigational smallpox vaccines. 4. Military service prior to 1991 or after January 2003. 5. Known or suspected significant underlying illness including, but not limited to, clinically significant liver disease, diabetes mellitus, or moderate to severe kidney impairment. 6. Malignancy (not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site) or history of skin cancer at the vaccination site. 7. Active autoimmune disease. Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded. 8. History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor\* \*Subjects with a not clinically relevant heart murmur, i.e., without any pathological ECG/arrhythmias or under treatment are not excluded. 9. Systolic blood pressure \>/= 150mmHg or diastolic blood pressure \>/= 100mmHg. 10. Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's (NCEP) risk assessment tool\* \*NOTE that this criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply: * have smoked a cigarette in the past month, and/or * have hypertension (defined as systolic blood pressure \>140 mm Hg) or are on antihypertensive medication, and/or * have a family history of coronary heart disease in male first-degree relative (father or brother) \<55 years of age or a female first-degree relative (mother or sister) \<65 years of age URL for NCEP risk assessment tool: http://cvdrisk.nhlbi.nih.gov/calculator.asp (if a subject has an HDL of greater than 100mg/dl please enter 100 in the tool) 11. High-dose corticosteroid use for greater than 2 weeks duration within three months prior to vaccination or current use of immunosuppressive medication: * \>5 mg prednisone or equivalent is considered high dose and immunosuppressive * Corticosteroid nasal sprays for allergic rhinitis are permissible * Persons who are using a topical steroid for mild uncomplicated dermatitis such as poison ivy or contact dermatitis may be enrolled the day after their therapy is completed * Inhaled steroids for asthma are not permissible * Oral/parenteral corticosteroids given for non-chronic conditions not expected to recur are permissible if the length of therapy was \</= 14 days with completion at least 30 days prior to enrollment. 12. Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol. 13. Any history of illegal injection drug use. 14. Receipt or planned receipt of inactivated vaccine from 14 days prior to the first vaccination through 14 days post second vaccination. 15. Receipt or planned receipt of any other live attenuated vaccine within 30 days prior to the first vaccination through 30 days post second vaccination. 16. Use of any other experimental agent within 30 days prior to vaccination and for the duration of the subject's participation in the study. 17. Receipt of blood products or immunoglobulin, including Rhogam, within six months prior to vaccination. 18. Donation of a unit of blood within 56 days prior to vaccination or planned donation prior to 28-days following the last vaccination. 19. Pregnant or breastfeeding women. 20. Active exfoliative skin disorders/conditions, current varicella zoster virus infection, or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2×2 cm. 21. Any condition that, in the opinion of the investigator, might interfere with assessing the study objectives. 22. Known allergy to egg, aminoglycoside (including gentamicin) or chicken. 23. Study personnel. 24. Allergic reaction to any vaccine.