Combination Study With MVA BN and Dryvax

Inclusion Criteria: Ages 18-32. Never received smallpox vaccination. Read, signed and dated informed consent document. Availability for follow-up for the planned duration of the study two years after first immunization. Acceptable medical history by screening evaluation and limited physical examination. For women, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination. If the volunteer is female and of child bearing potential, she agrees to use acceptable contraception, and not become pregnant for at least 56 days after the last vaccination. A woman is considered of child bearing potential unless post-menopausal or surgically sterilized. [Acceptable contraception methods are restricted to effective intrauterine devices (IUDs) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination.] Women who are not sexually active must agree to use one of the acceptable contraception methods if they are of childbearing potential. Negative ELISA for HIV. ALT<1.25 times institutional upper limit of normal. Negative hepatitis B surface antigen and negative antibody to hepatitis C virus. Negative urine glucose by dipstick or urinalysis. Adequate renal function defined as a serum creatinine less than or equal to 1.4mg/dL for males and less than or equal to 1.2mg/dL for females; urine protein < 30 mg/dL or none or trace proteinuria (by urinalysis or dipstick); and a calculated creatine clearance greater than or equal to 80 mL/min. based on the following formulas: Males [(140-age in years) X weight in kg]/(72 X serum creatinine) Females 0.85X[(140-age in years) X weight in kg]/(72 X serum creatinine) ECG without clinical significance (e.g., all kinds 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, or 2 premature ventricular contractions (PVC) in a row, or ST elevation consistent with ischemia) CBC: Hemoglobin >11g/dl; White blood cells greater than 2,500 and less than 11,000/cubic mm; Platelets greater than or equal to 140,000/cubic mm. Exclusion Criteria: History of immunodeficiency. Typical vaccinia scar. Known or suspected history of smallpox vaccination. Military service prior to 1989 or after January 2003. Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment. Malignancy, including squamous cell skin cancer or basal cell skin cancer at vaccination site or history of skin cancer at the vaccination site. Active autoimmune disease. Persons with vitiligo or thyroid disease on thyroid replacement are not excluded. History of keloid formation. History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor. 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 for Estimating Your 10-Year Risk of Having a Heart Attack, located at the following URL: http://hin.nhlbi.nih.gov/atpiii/calculator.asp. NOTE: This criterion applies only to volunteers 20 years of age and older. Abnormal troponin I. Use of immunosuppressive medication. Corticosteroid nasal sprays are permissible. Persons who have used topical steroid can be enrolled after their therapy is completed. Medical or psychiatric condition or occupational responsibilities that preclude volunteer compliance with the protocol. Any history of "illegal" injection drug use. Receipt of inactivated vaccine 14 days prior to vaccination. Receipt of live attenuated vaccines within 30 days of vaccination. Use of experimental agents within 30 days prior to vaccination. Receipt of blood products or immunoglobulin in the 6 months prior to vaccination. Acute febrile illness (greater than or equal to 100.5 degrees F) on the day of vaccination. Pregnant or lactating women. Eczema of any degree or history of eczema. People with atopic dermatitis, Varicella zoster, chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm. Household contacts/sexual contacts with, or occupational exposure to (other than minimal contact), any of the following: Pregnant women; Children <12 months of age; People with or history of eczema; People with atopic dermatitis, Varicella zoster, chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm; People with immunodeficiency disease or use of immunosuppressive medications. Any condition that, in the opinion of the investigator, might interfere with study objectives. Known allergies to or any component of MVA or MVA-BN vaccine (e.g., tris(hydroxymethl)-amino methane, sodium chloride, sucrose, dextran, L-Glutamic acid monopotassium, chicken embryo fibroblast proteins, gentamycin). Known allergy to egg or aminoglycoside. Known allergies to any component of the Dryvax® vaccine (e.g. polymyxin B sulfate, dihydrostreptomycin sulfate, chlorotetracycline hydrochloride, neomycin sulfate). Known allergies to any known component of the Dryvax® diluent (i.e. glycerin and phenol). Known allergies to any known components of vaccinia immunoglobulin (VIG), i.e. thimerosal or previous allergic reaction to immunoglobulins. Known allergies to cidofovir or probenecid. Study personnel.