Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination

The objective of this study is to determine the minimum dose of ACAM2000 that is calculated
to produce a major cutaneous reaction in at least 90% of a population of healthy adults 18-29
years of age and naïve to smallpox vaccine. Specifically, the objectives of this study are
to:

1. Compare the safety and tolerability of four dose levels of ACAM2000 and a standard dose
of Dryvax® in healthy adults 18-29 years of age and naïve to smallpox vaccine. Safety
and tolerability will be determined by examination of the local cutaneous reaction,
adverse events, physical examinations, vital signs, structured interviews, and
laboratory analysis.

2. Determine the immunogenicity of four dose levels of ACAM2000 and a standard dose of
Dryvax® in healthy adults 18-29 years of age by comparing:

1. the proportion of subjects at each dose level who develop a major cutaneous
reaction;

2. the proportion of subjects in each treatment group who develop neutralizing
antibodies, including the fold-increase in antibody titer between Baseline and Day
30 sera; and the geometric mean vaccinia neutralizing antibody titer on Day 30.

3. Determine the minimum dose of ACAM2000 that is calculated to produce a major cutaneous
reaction in at least 90% of a population of healthy adults 18-29 years of age and naïve
to smallpox vaccine.

Inclusion criteria:

- females must not be pregnant, lactating and must agree to use an effective form of
birth control for the 30 days following vaccination or unable to bear children.

- agree to be available for the entire study and agree to comply with all requirements.

Exclusion criteria:

- military service prior to 1989.

- history of previous smallpox vaccination.

- children 1 year of age or younger in the household or be in close contact

- smallpox vaccination within ten years

- known or suspected human immunodeficiency virus (HIV) infection, primary
immunodeficiency disorder, leukemia, lymphoma, or current radiation treatment or use
of immunosuppressive or anti-neoplastic drugs or have a household member or intimate
contact with the conditions listed above.

- renal disease

- current or past history of eczema or a household member or direct contact who has
eczema.

- known allergy or past allergic reactions to latex gloves or to antibiotics which
include neomycin, streptomycin, chlortetracycline, and polymyxin B

- known allergy or past allergic reaction to blood products.

- known allergy to cidofovir or sulfa-containing drugs.

- history of allergic phenomena following smallpox vaccination in the past, including
urticaria, erythema multiforme, or Stevens-Johnson syndrome.

- transfusion of blood or treatment with any blood product.

- current or history of drug or alcohol abuse

- inoculation with any other live vaccine or participating in another drug or vaccine
trial within 30 days of enrollment.