Phase I STEBVax in Healthy Adults

This study is a Phase I study of the safety and immunogenicity of recombinant Staphylococcal
Enterotoxin B vaccine (STEBVax) in healthy adults. STEBVax is a recombinant mutated form of
staphylococcal enterotoxin B (SEB) containing three point mutations that disrupt the
interaction of the toxin with human major histocompatibility complex (MHC) class II
receptors and render the protein non-toxic while retaining most of the immunogenicity. The
primary intended result of this program is the development of a hyperimmune serum for
treatment of toxic shock syndrome (TSS) originating from nosocomial, environmental or
potential bioterrorist events. An additional long-term goal is the development of a
multivalent vaccine and immunotherapeutic for treating or preventing diseases caused by
Staphylococcus (S.) aureus. The long-range goal is to develop a vaccine that will protect
against a broad range of staphylococcal superantigens. The primary objective is to evaluate
and assess the safety of parenterally administered STEBVax vaccine in healthy adult subjects
over a range of doses from 0.01 to 20 mcg by intramuscular injection. The secondary
objectives are to determine the immunogenicity of STEBVax vaccine over a range of doses as
determined by the rate and titer of seroconversion with serum anti-S. aureus enterotoxin B
IgG antibodies measured by enzyme-linked-immunosorbent serologic assay (ELISA). Participants
will include 28 healthy adult subjects from the University of Maryland Baltimore community.
Subjects will receive a dose of STEBVax in Alhydrogel adjuvant at one of the following
doses: 0.01, 0.1, 0.5, 2.5, 10 or 20 mcg or 2 doses of 20 mcg given 21 days apart. STEBVax
will be administered as a single 0.5 mL intramuscular injection. Subjects will be followed
for safety, reactogenicity, and immune response after vaccination. Subjects will be observed
in the clinic for at least 8 hours after vaccination and remain in the Baltimore-Washington
metropolitan area for 7 days after vaccination.

Inclusion Criteria:

- Ability to provide written informed consent.

- Age 18 - 40 years, inclusive.

- Good "general health" as determined by vital signs (heart rate <100 bpm; blood
pressure systolic > 90 mm Hg and less than or equal to 140 mm Hg; diastolic > 50 mm
Hg and less than or equal to 90 mm Hg; oral temperature <100.4 degrees Fahrenheit),
medical history, and a physical examination within 45 days before administration of
Recombinant Staphylococcal Enterotoxin B Vaccine (STEBVax). Blood pressure outside
this range may be repeated once on another occasion.

- Expressed interest and availability to fulfill the study requirements

- Agrees not to become pregnant from the time of study enrollment until at least 90
days after the last administration of STEBVax; if a woman is sexually active and
capable of conception (i.e., no history of hysterectomy or tubal ligation), she must
agree to use hormonal or barrier birth control such as implants, injectables,
combined oral contraceptives, some intrauterine devices (IUDs), condoms with
spermicidal agents, or must have a vasectomized partner, or must be sexually
abstinent. A woman is eligible if she is monogamous with a vasectomized male

- Agrees not to participate in another clinical trial at any time during the study
period.

- Agrees to remain in the Baltimore-Washington metropolitan area for 7 days after
vaccination.

Exclusion Criteria:

- History of any of the following medical illnesses:

- Toxic shock syndrome

- Asthma requiring daily prescription medication

- Psychiatric disorder requiring hospitalization

- Anaphylaxis/hypersensitivity reactions to glycine, or alum (vaccine components)

- Coagulopathy

- Kidney disease

- Diabetes

- Cancer

- Heart disease (hospitalization for a heart attack, arrhythmia, or syncope)

- Vascular disease (peripheral vascular disease, coronary artery disease, stroke)

- Arthritis

- Autoimmune disease (e.g., lupus erythematosis, rheumatoid arthritis)

- Unconsciousness (other than a single brief "concussion")

- Seizures (other than febrile seizures as a child <5 years old)

- Recurrent infections (more than 3 hospitalizations for invasive bacterial
infections such as pneumonia or meningitis)

- Any current illness requiring regular medication therapy other than vitamins or
birth control

- Any clinically significant abnormality including but not limited to:

- Murmur (other than a functional murmur)

- Focal neurological

- Hepatosplenomegaly

- Lymphadenopathy

- Jaundice

- Lab abnormality, as listed below. Toxicity grading scale provided in Appendix B,
Normal ranges provided in Appendix C. Laboratories with abnormalities possibly
transient in nature may be repeated one time.

- Hemoglobin, White blood cell count, Neutrophil count, or Platelet count outside
the normal range

- PT, PTT above the normal range

- Sodium, or potassium outside the normal range

- Creatinine above normal range

- Glucose outside the normal range (65 to <110 mg/dL is acceptable if non-fasting
test)

- AST, ALT, alkaline phosphatase, total bilirubin of grade 1 or greater on the
toxicity grading scale

- Urinalysis with proteinuria or hematuria

- Positive serology for hepatitis C or HIV antibody or hepatitis B surface antigen
(Subjects will be informed if their results are positive for hepatitis C, HIV
antibody or hepatitis B surface antigen and will be referred to a primary care
provider for follow up of these abnormal laboratory tests.)

- Have a positive urine drug screen.

- For women, positive serum pregnancy test within 45 days and urine pregnancy test
within 24 hours of administering STEBVax at days 0 and for the highest dose group who
receive two doses of vaccine, on day 21.

- Nursing mother

- Temperature > 38.0 degrees C (100.4 degrees F) or symptoms of an acute self-limited
illness such as an upper respiratory infection or gastroenteritis within 7 days
before administration of STEBVax

- Medical, occupational, or family problems as a result of alcohol or illicit drug use
during the past 12 months

- Failure to pass written examination (70 percent correct answers required to pass) on
the first attempt. (The exam is administered to assess and document comprehension of
the material presented which covers all aspects of the study including the purpose,
procedures, risks, benefits and pertinent microbiology).

- Receipt of an experimental agent (vaccine, drug, device, etc.) within 28 days before
administration of STEBVax or expects to receive an experimental agent during the
study period.

- Receipt of any licensed vaccine within 2 weeks (for inactivated vaccines) or 4 weeks
(for live vaccines) before vaccination in this study or expects to receive a licensed
vaccine before vaccination in this study.

- Known sensitivity to any ingredient in STEBVax (recombinant protein, glycine, sodium
chloride, alum)

- Prosthetic joint

- Receipt of immunoglobulin or other blood product within the 3 months prior to
vaccination in this study.

- Immunosuppression as a result of an underlying illness or treatment with
immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation
therapy within the preceding 36 months.

- Long-term use (> 2 weeks) of oral or parenteral steroids (glucocorticoids), or
high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or
equivalent) within the preceding 6 months (nasal and topical steroids are allowed).

- Other condition that in the opinion of the investigator would jeopardize the safety
or rights of a volunteer participating in the trial or would render the subject
unable to comply with the protocol.