A Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Healthy, Vaccinia-naïve Subjects

Inclusion Criteria:

- Male and female subjects, 18 to 40 years of age

- The subject has read, signed and dated the informed consent form, 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 procedures

- BMI ≥ 18.5 and < 35

- Women of childbearing potential (WOCBP) must have used an acceptable method of
contraception for 30 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 with a history of hysterectomy (Acceptable
contraception methods are restricted to abstinence, barrier contraceptives,
intrauterine contraceptive devices or licensed hormonal products)

- WOCBP must have a negative serum pregnancy test at screening and a negative urine
pregnancy test within 24 hours prior to each vaccination

- White blood cells ≥ 2,500/mm3 < ULN

- Absolute neutrophil count (ANC) within normal limits

- Hemoglobin within normal limits

- Platelets within normal limits

- Adequate renal function defined as a calculated Creatinine Clearance (CrCl) > 60
ml/min as estimated by the Cockcroft-Gault equation:

- For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl
x 72) = CrCl (ml/min)

- For women: multiply the result by 0.85 = CrCl (ml/min).

- Adequate hepatic function defined as:

- a. Total bilirubin ≤ 1.5 x ULN in the absence of other evidence of significant
liver disease

- b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
phosphatase ≤ 1.5 x ULN

- Troponin I < 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, AV 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

- Typical vaccinia scar

- Known or suspected history of smallpox vaccination

- History of vaccination with any poxvirus-based vaccine

- US Military service prior to 1991 or after January 2003

- Pregnant or breast-feeding women

- Uncontrolled serious infection, i.e. not responding to antimicrobial therapy

- History of any serious medical condition, which in the opinion of the investigator
would compromise the safety of the subject or would limit the subject's ability to
complete the trial

- History of or active autoimmune disease, persons with vitiligo or thyroid disease
taking thyroid replacement are not excluded

- Known or suspected impairment of immunologic function including, but not limited to,
HIV Infection, clinically significant liver disease (including chronic active HBV or
HCV), diabetes mellitus, moderate to severe kidney impairment

- History of malignancy other than squamous cell or basal cell skin cancer, unless there
has been surgical excision that is considered to have achieved cure. Subjects with
history of skin cancer must not be vaccinated at the previous tumor site

- History or clinical manifestation of clinically significant and severe hematological,
pulmonary, central nervous, cardiovascular or gastrointestinal disorders

- Clinically significant mental disorder not adequately controlled by medical treatment

- History of coronary heart disease, myocardial infarction, angina pectoris, congestive
heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high
blood pressure, or any other heart condition under the care of a doctor

- Known history of an immediate family member (father, mother, brother, or sister) who
has had onset of ischemic heart disease before age 50 years

- 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 risk
assessment tool (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof) NOTE:
This criterion applies only to subjects 20 years of age and older

- Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse
(within the past 6 months)

- Known allergy to IMVAMUNE® vaccine and its constituents, e.g. tris
(hydroxymethyl)-amino methane, including know allergy to egg or aminoglycosides

- History of anaphylaxis or severe allergic reaction to any vaccine

- Acute disease (illness with or without a fever) at the time enrollment

- Body temperature ≥100.4°F (≥38.0°C) at the time of enrollment

- Having received any vaccinations or planned vaccinations with a live vaccine within 30
days prior to or after trial vaccination

- Having received any vaccinations or planned vaccinations with a killed vaccine within
14 days prior to or after trial vaccination

- Chronic systemic administration (defined as more than 14 days) of > 5 mg prednisone
(or equivalent)/day or any other immune-modifying drugs during a period starting from
three months prior to administration of the vaccine and ending at last physical trial
visit (V5)

- Post organ transplant subjects whether or not receiving chronic immunosuppressive
therapy

- Administration or planned administration of immunoglobulins and/or any blood products
during a period starting from three months prior to administration of the vaccine and
ending at last physical trial visit (V5)

- Use of any investigational or non-registered drug or vaccine other than the trial
vaccine within 30 days preceding the first dose of the trial vaccine, or planned
administration of such a drug during the trial period

- Trial personnel