Safety, Tolerability and Immune Response of IMVAMUNE (MVA-BN)Smallpox Vaccine in HIV Infected Patients

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.