Phase I/II Trial of Modified Vaccinia Virus Ankara (MVA) Vaccine Against Smallpox

INCLUSION CRITERIA: A participant must meet all of the inclusion criteria, as follows: 1. Age born no later than 1979 - age 60 years old 2. Prior vaccination more than 10 years ago with any vaccinia product and evidence of a scar typical of prior vaccination leading to a primary take. 3. Available for follow-up for the duration of the study (at least 28 weeks). 4. Able and willing to sign the informed consent form 5. Willing to allow blood samples to be stored for future research 6. In good general health, without clinically significant medical history, physical examination findings or laboratory results. 7. Hematocrit greater than or equal to 34% for women; greater than or equal to 38% for men 8. White blood cell count within institutional normal limits 9. Differential either within institutional normal range or accompanied by site physician approval 10. Total lymphocyte count greater than or equal to 1000 cells/mm(3) 11. Absolute CD4 count greater than or equal to 400 cells/mm(3) 12. Platelets within institutional normal limits 13. ALT (SGPT) less than or equal to institutional upper normal limit 14. Serum creatinine less than or equal to 1.3 mg/dL and calculated creatinine clearance (CrCl) greater than or equal 55 mL/min using the formula below: Male CrCl (mL/min) = \[140 - age (yrs)\] x \[body wt (kg)\] / 72 x \[serum Cr (mg/dL)\] Female CrCl (mL/min) = \[140 - age (yrs)\] x \[body wt (kg) x .85\] / 72 x \[serum Cr (mg/dL)\] 15. Normal urinalysis defined as: negative glucose, negative or trace protein, and negative or trace hemoglobin 16. Negative hepatitis B surface antigen (HBsAg) 17. Negative anti-HCV or negative HCV PCR if the anti-HCV is positive 18. Negative HIV ELISA and HIV PCR (volunteers who have previously participated in an HIV vaccine study are eligible with positive ELISA if Western blot is indeterminate or negative and HIV PCR is negative.) 19. Negative serum beta-HCG test for women presumed to be of reproductive potential. 20. A female participant must meet one of the following criteria: a) no reproductive potential due to menopause (one year without menses), hysterectomy, bilateral oophorectomy, or tubal ligation; b) agrees to consistently practice contraception at least 30 days prior to enrollment and throughout the duration of the study by means of IUD, hormone-based therapy (e.g., contraceptive pills, Norplant (Registered Trademark), or Depo-Provera (Registered Trademark)) or other FDA-licensed methods). 21. Able to provide proof of identity to the acceptance of the study clinician completing the enrollment process. EXCLUSION CRITERIA: Volunteers are excluded from study participation if one or more of the following is true: 1. Vaccination with any vaccinia product within the last 10 years including vaccination with any vaccinia recombinant product. 2. Diseases or conditions that cause immunodeficiency (examples are HIV AIDS, leukemia, lymphoma, generalized malignancy, agammaglobulinemia, history of transplantation, or therapy with alkylating agents, antimetabolites, radiation, or oral or parental corticosteroids). 3. In close physical contact (household or at work) with an individual who has the diseases or conditions that cause immunodeficiency. 4. History of eczema, even if the condition is mild or not presently active. 5. In close physical contact (household or at work) with an individual who has eczema, even if mild or not presently active. 6. Acute or chronic skin conditions such as atopic dermatitis, burns, impetigo, or varicella zoster (shingles). 7. Household member who is pregnant. 8. Women who are breast-feeding. 9. Household member less than 1 year old or work with children less than 1 year old. 10. Serious, life-threatening allergies to antibiotics polymixin B, streptomycin, tetracycline, neomycin or cidofovir. 11. Allergy to eggs or blood products (including Immunoglobulin products) or hypersensitivity to probenicid or sulfa-containing medications. 12. Receipt of live attenuated viruses within 30 days prior to enrollment. 13. Receipt of subunit or killed vaccines within 14 days prior to enrollment. 14. Use of investigational research agents within 30 days prior to enrollment. 15. Receipt of blood products within 120 days prior to HIV screening. 16. Receipt of immunoglobulin within 60 days prior to HIV screening. 17. History of serious adverse reactions to vaccines, such as anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema and abdominal pain. 18. History of type I or type II diabetes mellitus, except gestational diabetes or diabetes controlled with diet alone. 19. Currently taking anti-TB prophylaxis or therapy. 20. History of seizure disorder other than: a) febrile seizures under the age of two, or b) seizures secondary to alcohol withdrawal more than 3 years ago, or c) a singular seizure more than 3 years ago. 21. Bleeding disorder that was diagnosed by a physician, (e.g., factor deficiency, coagulopathy, or platelet disorder that requires special precautions). 22. Splenectomy. 23. Hypertension that is not well controlled by medication or is more than 150/100 at enrollment. 24. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well-controlled on medication within the past two years; disorder requiring lithium; suicidal ideation occurring within five years prior to enrollment. 25. Any medical, psychiatric, social condition, or occupational or other responsibility that, in the judgement of the investigator, would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent. 26. History of cardiomyopathy, myocardial infarction, angina, congestive heart failure, coronary artery disease, stroke, transient ischemic attack, or history of 3 or more risk factors for coronary heart disease from the following list: current cigarette smoking; high blood pressure diagnosed by a doctor; high blood cholesterol diagnosed by a dicotr or a fasting LDL greater than 160 mg/dL at screening; diabetes diagnosed by a doctor; a first-degree relative (father, mother, brother, sister) who had coronary artery disease before the age of 50.