Inclusion Criteria:

• Male subjects between 18 and 49 years of age or female subjects between 18 and 55 years of age who provided informed consent.
• Women with negative pregnancy test.
• Women of childbearing potential must use an acceptable method of contraception.
• Cardiac enzymes within ULN.
• White blood cells ≥ 2500/mm3 and < 11,000/ mm3.
• Absolute neutrophil count ≥ 1000/mm3.
• Adequate renal function.
• Adequate hepatic function.
• Negative hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
• Negative antibody test to hepatitis C virus (HCV).
• Negative urine glucose by dipstick or urinalysis.
• Normal 12-lead electrocardiogram.
• Availability for follow-up during the study.

Groups 1 and 3 (All vaccinia-naïve subjects) additionally:

• No history of known or suspected previous smallpox vaccination.
• No detectable vaccinia scar.
• No military service prior to 1989 or after January 2003.

Groups 2 and 4 (All previously vaccinated subjects) additionally:

• History of at least one previous smallpox vaccination
• Time since most current smallpox vaccination > 10 years.

Groups 1 and 2 (All HIV Infected subjects) additionally:

• Documented HIV-1 infection
• Plasma HIV-1 RNA level < 400 copies/mL at screening.
• CD4 cells ≥ 350/µL
• Haemoglobin ≥ 9.0 g/dL.
• Platelets ≥ 100,000/mm3.
• AST (SGOT), ALT (SGPT) and alkaline phosphatase ≤ 3 x ULN

Groups 3 and 4 (All Healthy subjects) additionally:

• Negative ELISA for HIV.
• Haemoglobin >11 g/dL.
• Platelets ≥ 140,000/mm3.
• AST (SGOT), ALT (SGPT) and alkaline phosphatase without clinically significant findings

Exclusion Criteria:

• Pregnant or breast-feeding women.
• Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
• History of any serious medical condition (other than HIV infection).
• History of or active autoimmune disease.
• Known or suspected impairment of immunologic function (other than HIV infection).
• History of malignancy.
• History or clinical manifestation of clinically significant and severe haematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
• Clinically significant mental disorder not adequately controlled by medical treatment.
• Any condition which might interfere with study objectives.
• History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.
• History of an immediate family member with onset of ischemic heart disease before age 50.
• 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.
• History of chronic alcohol abuse and/or intravenous drug abuse.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Known previous allergic reaction to immunoglobulins.
• Known allergies to cidofovir or probenecid.
• History of anaphylaxis or severe allergic reaction.
• Acute disease (illness with or without a fever) at the time of enrollment.
• Temperature >100.4°F at the time of enrollment.
• Subjects undergoing treatment for tuberculosis infection or disease.
• Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after study vaccination.
• Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior or after study vaccination.
• Chronic administration of immuno-suppressant or immune-modifying drugs.
• Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.
• Administration or planned administration of immunoglobulins and/or any blood products.
• Use of any investigational or non-registered drug or vaccine.