The overall goals of this study are to expand the available data on the safety and
immunogenicity of MVA-BN in vaccinia-naive adults and to determine the optimum dose of
MVA-BN to induce immune responses and attenuate Dryvax take reactions. Participants will
include 90 healthy volunteers, ages 18-32 years. Participants will be randomly assigned to 1
of 6 study groups (groups A-F). Participants will be involved in study related procedures
for up to 2 years. During this time, volunteers will return periodically for blood draws to
check immune responses.
The primary goal of this phase I trial is to expand the available data on the safety and
immunogenicity of MVA-BN in vaccinia-naïve adults. The secondary goals of this vaccine trial
are: to determine the optimum dose of MVA-BN, given twice, to induce an immune response and
attenuate Dryvax® take reactions; and to compare the ability of 2 routes of administration
of MVA-BN, subcutaneous and intramuscular, to induce an immune response at the highest
tested dose. A total of 90 healthy adult volunteers ages 18-32 will participate in this
study. The volunteers will be randomly assigned to 1 of 6 groups to be immunized with:
MVA-BN (subcutaneously) at 1 of 3 dose levels and Dryvax® (per scarification); placebo
(subcutaneously) and Dryvax® (per scarification); MVA-BN (subcutaneously) at the highest
dose level and placebo scarification; or MVA-BN (intramuscularly) at the highest dose level
and Dryvax® (per scarification). The study will last about 30 months. Each volunteer's
participation will last 6 months for all treatment groups. Subjects randomized to treatment
groups D and E will have follow-up for 2 years. During this time, volunteers will return
periodically for blood draws to check immune responses. Subjects will require visits for
dressing changes as needed post-Dryvax vaccination. Variables to be investigated include:
adverse events and side effects to the vaccines, and immunogenicity testing including
antibody and cellular responses to the vaccines.
- Ages 18-32.
- Never received smallpox vaccination.
- Read, signed and dated informed consent document.
- Availability for follow-up for the planned duration of the study two years after
- Acceptable medical history by screening evaluation and limited physical examination.
- For women, negative serum pregnancy test at screening and negative urine or serum
pregnancy test within 24 hours prior to vaccination.
- If the volunteer is female and of child bearing potential, she agrees to use
acceptable contraception, and not become pregnant for at least 56 days after the last
vaccination. A woman is considered of child bearing potential unless post-menopausal
or surgically sterilized. [Acceptable contraception methods are restricted to
effective intrauterine devices (IUDs) or licensed hormonal products with use of
method for a minimum of 30 days prior to vaccination.] Women who are not sexually
active must agree to use one of the acceptable contraception methods if they are of
- Negative ELISA for HIV.
- ALT<1.25 times institutional upper limit of normal.
- Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
- Negative urine glucose by dipstick or urinalysis.
- Adequate renal function defined as a serum creatinine less than or equal to 1.4mg/dL
for males and less than or equal to 1.2mg/dL for females; urine protein < 30 mg/dL or
none or trace proteinuria (by urinalysis or dipstick); and a calculated creatine
clearance greater than or equal to 80 mL/min. based on the following formulas:
- Males [(140-age in years) X weight in kg]/(72 X serum creatinine)
- Females 0.85X[(140-age in years) X weight in kg]/(72 X serum creatinine)
- ECG without clinical significance (e.g., all kinds of atrioventricular or
intraventricular conditions or blocks such as complete left or right bundle branch
block, AV-node block, QTc or PR prolongation, premature atrial contractions or other
atrial arrhythmia, sustained ventricular arrhythmia, or 2 premature ventricular
contractions (PVC) in a row, or ST elevation consistent with ischemia)
- CBC: Hemoglobin >11g/dl; White blood cells greater than 2,500 and less than
11,000/cubic mm; Platelets greater than or equal to 140,000/cubic mm.
- History of immunodeficiency.
- Typical vaccinia scar.
- Known or suspected history of smallpox vaccination.
- Military service prior to 1989 or after January 2003.
- Known or suspected impairment of immunologic function including, but not limited to,
clinically significant liver disease; diabetes mellitus; moderate to severe kidney
- Malignancy, including squamous cell skin cancer or basal cell skin cancer at
vaccination site or history of skin cancer at the vaccination site.
- Active autoimmune disease. Persons with vitiligo or thyroid disease on thyroid
replacement are not excluded.
- History of keloid formation.
- History of myocardial infarction, angina, congestive heart failure, cardiomyopathy,
stroke or transient ischemic attack, or other heart condition under the care of a
- History of an immediate family member (father, mother, brother or sister) who has had
onset of ischemic heart disease before age 50 years.
- 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 for Estimating Your 10-Year Risk of Having a Heart Attack, located at
the following URL: http://hin.nhlbi.nih.gov/atpiii/calculator.asp. NOTE: This
criterion applies only to volunteers 20 years of age and older.
- Abnormal troponin I.
- Use of immunosuppressive medication. Corticosteroid nasal sprays are permissible.
Persons who have used topical steroid can be enrolled after their therapy is
- Medical or psychiatric condition or occupational responsibilities that preclude
volunteer compliance with the protocol.
- Any history of "illegal" injection drug use.
- Receipt of inactivated vaccine 14 days prior to vaccination.
- Receipt of live attenuated vaccines within 30 days of vaccination.
- Use of experimental agents within 30 days prior to vaccination.
- Receipt of blood products or immunoglobulin in the 6 months prior to vaccination.
- Acute febrile illness (greater than or equal to 100.5 degrees F) on the day of
- Pregnant or lactating women.
- Eczema of any degree or history of eczema.
- People with atopic dermatitis, Varicella zoster, chronic exfoliative skin
disorders/conditions or any acute skin disorders of large magnitude, e.g., laceration
requiring sutures, burn greater than 2x2 cm.
- Household contacts/sexual contacts with, or occupational exposure to (other than
minimal contact), any of the following: Pregnant women; Children <12 months of age;
People with or history of eczema; People with atopic dermatitis, Varicella zoster,
chronic exfoliative skin disorders/conditions or any acute skin disorders of large
magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm; People with
immunodeficiency disease or use of immunosuppressive medications.
- Any condition that, in the opinion of the investigator, might interfere with study
- Known allergies to or any component of MVA or MVA-BN vaccine (e.g.,
tris(hydroxymethl)-amino methane, sodium chloride, sucrose, dextran, L-Glutamic acid
monopotassium, chicken embryo fibroblast proteins, gentamycin).
- Known allergy to egg or aminoglycoside.
- Known allergies to any component of the Dryvax® vaccine (e.g. polymyxin B sulfate,
dihydrostreptomycin sulfate, chlorotetracycline hydrochloride, neomycin sulfate).
- Known allergies to any known component of the Dryvax® diluent (i.e. glycerin and
- Known allergies to any known components of vaccinia immunoglobulin (VIG), i.e.
thimerosal or previous allergic reaction to immunoglobulins.
- Known allergies to cidofovir or probenecid.
- Study personnel.