ACAM 3000 MVA at Harvard Medical School

Inclusion Criteria: General: * Age: greater than or equal to 18 and born after 1971. * Complete a written assessment of understanding prior to enrollment and verbalize understanding of all questions answered incorrectly. * Informed consent: Be able, willing, and have signed the informed consent form. * Health: Be in good general health without clinically significant medical history, physical examination findings, or clinically significant abnormal laboratory results. A clinically significant condition or process includes one or more of the following: a) A condition that is chronic or recurring and is life threatening b) A process that would affect the immune response c) A process that would require medication that affects the immune response d) A condition for which repeated injections or blood draws may pose additional risk to the participant e) A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being f) A condition or process in which signs or symptoms could be confused with reactions to vaccine Laboratory: * Willing to have blood samples stored for future smallpox related research. * Hematology and chemistries within institutional normal limits for age and sex for the following: hemoglobin, white blood cell (WBC)\], serum creatinine, platelets, troponin, alanine aminotransferase (ALT) \[within 1.25 under normal limits (ULN), aspartate aminotransferase (AST) (within 1.25 ULN), alkaline phos (within 1.25 ULN), total bilirubin (within 1.25 ULN). * Negative for Hepatitis B surface antigen and Hepatitis C virus (HCV) antibodies \[If HCV antibodies are positive, and negative for HCV by polymerase chain reaction (PCR), subject is eligible\] * Negative FDA-approved human immunodeficiency virus (HIV) blood test within 8 weeks prior to enrollment * Normal urine dipstick or urinalysis: 1. Negative glucose, and 2. Negative or trace protein and negative or trace hemoglobin (if trace hemoglobin is present, a urinalysis is required to exclude participants with counts greater than the institutional normal range) In addition to meeting ALL of the above criteria, FEMALE participants must meet BOTH of the following criteria: * Negative serum or urine beta-human chorionic gonadotropin (HCG) pregnancy test performed within 24 hours prior to any vaccination. * Reproductive status: A female participant either must: 1. not be of reproductive potential. Reproductive potential in women is defined as not having reached menopause (no menses for one year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation. 2. be with a male partner(s) throughout the duration of the study who has undergone successful vasectomy (A vasectomy is considered successful if a woman reports that a male partner has (1) microscopic documentation of azospermia, or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post-vasectomy.), or 3. agree to avoid pregnancy through alternative methods and agree to consistently use contraception for at least 21 days prior to enrollment until the last protocol visit. Contraception is defined as using one of the following methods: i) condoms (male or female with or without a spermicide) ii) diaphragm or cervical cap with spermicide iii) intrauterine device (IUD) iv) hormone-based therapy, e.g., contraceptive pills, Norplant, or Depo-Provera In addition to the above criteria, female participants must meet the following criteria prior to participating in Dryvax vaccination: * Negative serum or urine beta-HCG pregnancy test performed within 24 hrs prior to vaccination. * Comply with one of the following methods of contraception for at least 21 days prior to vaccination and at least 2 months post vaccination. 1. Hormonal contraception: such as implants, injectables, combined oral contraceptives 2. Not be of reproductive potential: this may be due to i) Hysterectomy or tubal ligation ii) The participant is in a monogamous relationship with a male partner who has undergone successful vasectomy (Successful vasectomy as defined as microscopic documentation of azospermia or a vasectomy more than two years ago with no resultant pregnancy despite sexual activity post-vasectomy.) c) Sexual abstinence Exclusion Criteria: * Prior vaccination with a vaccinia product. Determined by clinical evidence of scarification or self-reported history of vaccinia vaccination (such as in the United States military before 1991 or after 2003). * Immunosuppressive medications within 168 days prior to initial study vaccine administration, e.g., oral/parenteral corticosteroids, and/or cytotoxic medications. Not excluded: A participant using any of the following is not excluded: corticosteroid nasal spray for allergic rhinitis; or topical corticosteroids as prescribed by a physician for an acute, uncomplicated dermatitis; or over the counter medications (including topical corticosteroids for an acute, uncomplicated dermatitis); use of rapidly tapered steroids for an acute isolated condition, which does not include asthma within 28 days prior to vaccine administration. * Currently using corticosteroid eye drops. * Receipt of blood products within 120 days prior to initial study vaccine administration. * Receipt of immunoglobulin within 60 days prior to initial study vaccine administration. * Receipt of live attenuated vaccines within 30 days prior to initial study vaccine administration. * Receipt of investigational research agents within 30 days prior to initial study vaccine administration. * Receipt of medically indicated subunit or killed vaccines, e.g., influenza, pneumococcal, or allergy treatment with antigen injections within 14 days prior to initial study vaccine administration. Participant has a history of any of the following: * Acute febrile illness on the day of vaccination. * Eczema or atopic dermatitis (past or present). * Chronic exfoliative skin condition. * Acute skin disorders of large magnitude (greater than 2x2 centimeters), e.g., burns or lacerations. * History or presence of skin cancer at vaccination site. * Heart disease including history of a myocardial infarction (MI), angina, congestive heart failure (CHF), or pericardial pathology. * 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: This criterion applies only to subjects 20 years of age and older AND only if at least one of the following applies: a) have smoked a cigarette in the past month, and/or b) have hypertension (defined as systolic blood pressure greater than 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) less than 55 years of age or a female first-degree relative (mother or sister) less than 65 years of age. * Household contacts/sexual contacts with, or frequent and/or prolonged exposure to any of the following: a) Children less than 12 months of age b) Pregnant women or women who are breast feeding c) Individuals with a history of eczema or atopic dermatitis d) Individuals with chronic exfoliative skin disorders or skin disorders of large magnitude (greater than 2x2 centimeters) e) Individuals with an immunosuppressive disorder such as HIV infection, organ transplantation, or a condition requiring prolonged corticosteroid therapy * Electrocardiogram (ECG) with clinically significant findings, or features that would interfere with the assessment of myo/pericarditis as determined by the consulting cardiologist, including any of the following: (1) Conduction disturbance (complete left or incomplete right bundle branch block or nonspecific intraventricular conduction disturbance with waves of ventricular activity of the heart traced on an ECG (QRS) greater than 120 millisecond (ms), atrioventricular (AV) block of any degree, or QTc prolongation (greater than 440 ms); (2) Repolarization (ST segment or T wave) abnormality; (3) Significant atrial or ventricular arrhythmia; (4) Frequent atrial or ventricular ectopy (e.g. frequent premature atrial contractions, 2 premature ventricular contractions in a row); (5) ST elevation consistent with ischemia; (6) Evidence of past or evolving myocardial infarction. * Known or suspected allergy to any component of the vaccine or diluent. * Allergy to eggs or blood products \[including immunoglobulin (IgG) or vaccinia immunoglobulin\]. * Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. Not excluded: A participant who had an adverse reaction to pertussis vaccine as a child is not excluded. * Autoimmune disease. * Immunodeficiency. * Asthma that is unstable, e.g., use of oral or intravenous corticosteroids, hospitalization or intubation during the past 2 years a) Inhaled steroids are not permissible * Diabetes mellitus type I or type II including cases controlled with diet alone. Not excluded: A participant with past gestational diabetes is not excluded. * Bleeding disorder diagnosed by a doctor, e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions. Not excluded: A participant who states he/she has easy bruising or bleeding, but does not carry a formal diagnosis and has had intramuscular (IM) injections and blood draws without any adverse experience, is not excluded. * Seizure disorder not excluded: A participant with a remote history (over 3 years ago) of seizure who has not required medications for over 3 years is not excluded if (a) the seizures were febrile seizures under the age of 2, or (b) secondary to alcohol withdrawal, or (c) if the seizure only occurred once. * Asplenia. Any condition resulting in the absence or removal of the spleen. * Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with one or more of the following: a) Psychoses within the past 5 years. b) Suicidal ideation occurring within 2 years prior to enrollment. Not excluded: A participant with a remote history (greater than 3 years) of a suicide attempt or suicide gesture is not excluded if the investigator finds the participant (a) to be of sound mental health; and (b) the suicide attempt was a well-defined, isolated event; and (c) the cause or inciting factor(s) no longer has relevance to the individual. A participant currently in therapy, due to a suicide attempt or gesture, or suicidal ideation, may be enrolled only when the participant's current therapist or health care provider provides documentation that the participant currently is not suicidal. * Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or a participant's ability to give informed consent. * Female participants: Participant is pregnant and/or breast-feeding. In addition to the above criteria, the following exclusion criteria apply to those participants consenting to Dryvax vaccination: -A history of the following: 1. Excessive scarring 2. Known or suspected allergy to any component of the vaccine or diluent including polymyxin B sulfate, dihydrostreptomycin sulfate, chlorotetracycline hydrochloride, neomycin, and phenol. 3. Known allergy to cidofovir or probenecid -Abnormal renal function: a) A calculated creatinine clearance less than 80 mL/min based on the following formulas: i) Males: \[(140 - age in years) X weight in kilograms (kg)\]/(72 X serum creatinine) ii) Females: 0.85 X \[(140 - age in years) X weight in kg\]/(72 X serum creatinine)