High Dose IMVAMUNE® in Vaccinia-Naive Individuals

Inclusion Criteria

Prior to initial vaccination: -At least 18 years of age and born after 1971 -Read, sign, and date informed consent document -Available for follow-up for the planned duration of the study (six months after last immunization) -Acceptable medical history by screening evaluation and limited physical assessment -If the subject is female and of childbearing potential, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination -If the subject is female and of childbearing potential, she agrees to use acceptable contraception, and not become pregnant for 28 days following the last vaccination a. A woman is considered of childbearing potential unless post-menopausal (> 1 year) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy) b. 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, abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus), and monogamous relationship with a vasectomized partner. -Negative enzyme linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) -Alanine aminotransferase (ALT) /= 150 mmHg or diastolic blood pressure >/= 100 mmHg. -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) NOTE that this criterion applies only to subjects 20 years of age and older and only if at least one of the following apply: a. Have smoked a cigarette in the past month, and/or b. Have hypertension (defined as systolic blood pressure >140 mm Hg) or are on antihypertensive medication, and/or c. Have a family history of coronary heart disease in male first-degree relative (father or brother) /= 150 mmHg or diastolic blood pressure >/=100 mmHg -High-dose steroid use for greater than 2 weeks duration within three months prior to vaccination and current use of immunosuppressive medication. a. Corticosteroid nasal sprays are permissible b. Persons who are using a topical steroid can be enrolled after their therapy is completed c. Inhaled steroids for asthma are not permissible -Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol -Any history of illegal injection drug use -Receipt or planned receipt of inactivated vaccine from 14 days prior to vaccination through 14 days post second vaccination -Receipt or planned receipt of any other live attenuated vaccine from 30 days prior to vaccination through 30 days post second vaccination -Use of any other experimental agent within 30 days prior to vaccination and for the duration of the study -Receipt of blood products or immunoglobulin within six months prior to vaccination -Donation of a unit of blood within 56 days prior to vaccination or prior to Visit 9 -Acute febrile illness (greater than or equal to 100.4 degrees Fahrenheit) on the day of vaccination -Pregnant or lactating women -Eczema of any degree or history of eczema -People with active atopic dermatitis, active exfoliative skin disorders/conditions, current Varicella zoster, or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2×2 cm -Any condition that, in the opinion of the investigator, might interfere with study objectives -Known allergy to IMVAMUNE® vaccine -Known allergy to egg or aminoglycoside (including gentamicin)