A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of MVA-BN in a Dose Response Regimen Followed by Administration of Dryvax in Healthy Adult Volunteers

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.