Take Rate, Immunogenicity and Safety of Elstree-BN Smallpox Vaccine in Healthy Vaccinia-Naive Subjects

Phase I Study to Evaluate Take Rate, Immunogenicity and Safety of Bavarian Nordic's Smallpox Vaccine Elstree-BN Administered to Healthy Vaccinia-Naive Subjects in the Age of 18-32 Years

The purpose of this study is to assess the take rate (formation of a typical postvaccinal lesion)and the safety and immunogenicity of the smallpox vaccine Elstree-BN.

Inclusion Criteria:

• Signed informed consent
• Free of obvious health problems
• Negative HIV test
• Negative hepatitis B surface antigen and negative antibody to hepatitis C virus
• Hematocrit ≥ 38%; white blood cells between 4.0 and 10.0 / nl with differential blood count without clinical finding; and platelets between 150 and 400 / nl
• ALT < 1.5 times institutional upper limit of normal
• Negative urine glucose by dipstick or urinalysis
• Adequate renal function defined as a serum creatinine < 1.5 mg/dL; urine protein < 100 mg/dL or < 2+ proteinuria; and a calculated creatinine clearance > 55 mL/min.
• For women, negative pregnancy test at screening and within 24 hours prior to vaccination.
• If the volunteer is female and of childbearing potential, she agrees to use acceptable contraception.

Exclusion Criteria:

• Pregnancy or breast-feeding

• Known or suspected history of smallpox vaccination

• Typical vaccinia scar

• Vaccinia specific antibodies at screening

• History of immunodeficiency

• Known or suspected impairment of immunologic function

• Use of immunosuppressive medication or radiation therapy

• Any history of atopic disease

• Eczema of any degree or history of eczema

• Chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude

• Any malignancy including leukemia or lymphoma

• Presence of any infectious disease or a history or evidence of autoimmune disease

• History or clinical manifestation of clinically significant mental illness or haematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders

• History of drug or chemical abuse

• Administration of inactivated vaccine 14 days prior to vaccination

• Any immune modifying therapy within 4 weeks prior to vaccination

• Administration of live attenuated vaccines within 60 days prior to vaccination

• Receipt of blood products or immunoglobulin in the past 6 months

• Subjects with acute febrile illness within one week prior to vaccination or subjects who may be in the incubation period of an infectious disease

• Household contacts/sexual contacts with, or occupational exposure to any of the following:

  1. Pregnant women
  2. Children <12 months of age
  3. People with current or history of atopic dermatitis
  4. People with chronic exfoliative skin disorders/conditions or any acute skin disorders
  5. People with immunodeficiency disease, malignancies or use of immunosuppressive medications

• History of anaphylaxis or severe allergic reaction

• Hypersensitivity to egg or chick protein

• Known allergies to any component of the vaccine or its diluent

• Known allergies to any known component of VIG

• Known allergies to cidofovir or probenecid

• Abnormalities suggestive of any underlying disease, detected at routine tests prior to study inclusion

• Use of any investigational or non-registered drug or vaccine starting 30 days preceding the study vaccine and ending at conclusion visit

• History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor.

• Three or more of the following risk factors: An immediate family member who has had onset of ischemic heart disease before age 50 years, elevated blood pressure, elevated blood cholesterol, diabetes or nicotine abuse.