A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000®

Inclusion Criteria

• Healthy male and female subjects, 18-42 years of age
• The subject has read, signed and dated the Informed Consent, having been advised of the risks and benefits of the trial in a language understood by the subject and prior to performance of any trial specific procedure
• Acceptable medical history by screening evaluation and physical examination
• BMI greater or eaqual than 18.5 and smaller than 35
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening and a negative urine or serum pregnancy test within 24 hours prior to each vaccination
• WOCBP must have used an acceptable method of contraception for 28 days prior to the first vaccination, must agree to use an acceptable method of contraception during the trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products)
• Human Immunodeficiency Virus (HIV) antibody negative, hepatitis B surface antigen negative and negative antibody test to hepatitis C virus
• White blood cells greater or eaqual than 2500/mm3 and smaller than 11,000/mm3
• Hemoglobin within normal limits
• Platelets greater or eaqual than lower normal limits
• Adequate renal function defined as a calculated Creatinine Clearance (CrCl) greater than 60 ml/min as estimated by the Cockcroft-Gault equation
• Adequate hepatic function in the absence of other evidence of significant liver disease defined as:
• Total bilirubin greater than 1.5 x Upper Limit Normal (ULN)
• Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) greater than 1.5 x ULN
• Alkaline Phosphatase (Alk Phos) greater than 1.5 x ULN
• Troponin I smaller than 2 x ULN
• Electrocardiogram (ECG) without clinically significant findings, e.g. any kind of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, atrioventricular node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, two premature ventricular contractions in a row, ST elevation consistent with ischemia

Exclusion Criteria

• Pregnant or breast-feeding women
• Typical vaccinia scar
• Known or suspected history of smallpox vaccination defined as visible vaccination scar or documentation of smallpox vaccination or as reported by the subject
• History of vaccination with any poxvirus-based vaccine
• History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject
• History of or active immunodeficiency or immunosuppression caused by acquired or congenital diseases or caused by ongoing treatments such as chronic (greater than 14 days) high-dose corticosteroids (smaller than 5 mg prednisone [or equivalent] per day applied systemically, i.e. parenterally or orally), chronic or planned treatment with steroid eye drops or ointment at time of enrollment or radiation, or immunosuppressive drugs; low-dose corticosteroid topical products and nasal sprays used sporadically, i.e. pro re nata (according to circumstances) are permissible
• Having had radiation or X-ray treatment (not routine X-rays) within the last 3 months
• Post organ and bone-marrow transplant subjects whether or not receiving chronic immunosuppressive therapy
• Eye surgery within 4 weeks prior to trial vaccination
• History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded
• Uncontrolled serious infection, i.e. not responding to antimicrobial therapy
• History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision considered to have achieved cure