Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial

Staphylococcus aureus is a leading cause of skin and soft tissue infections. Antibiotic
resistance, such as seen with new community-acquired methicillin-resistant strains, presents
a major challenge in treating and preventing these infections. Therefore, a preventative
vaccine is considered a potentially better approach.

This study assesses the safety and immunogenicity of monovalent and bivalent S. aureus
vaccine components. Healthy adult subjects will be randomized to receive 1 dose of monovalent
or bivalent toxoid vaccine, or placebo in a dose escalation schedule.

Antigen-specific antibody will be measured by ELISA in sera collected for three months after
injection. Safety data will be collected as 7 day reactogenicity diaries after each
injection, adverse events and Staphylococcus aureus and skin and soft tissue infections will
be collected through Day 84, and serious adverse events and chronic illnesses will be
collected for the full 6 month study period.

To evaluate the possible utility of booster doses, the cohort receiving the highest dose of
bivalent antigen will have a 2nd dose administered at Day 84, with a new 7-day reactogenicity
diary and sera collected after the 2nd dose. All subjects will be followed up with a 6 month
phone call after vaccination or booster.

The total subject observation period will be for 24 weeks from Day 0, plus 12 additional
weeks for the cohorts that receive a 2nd dose. With a recruitment period of 4 months, the
study duration is expected to be approximately 13 months.

Inclusion Criteria:

- Healthy adult males or females, DoD beneficiaries, including active duty members,
18-55 years of age.

- Negative urine pregnancy test for female subjects of child bearing potential (negative
test within 24 hours prior to investigational product injection) or documented
surgical sterility.

- Female subjects of child-bearing potential must use an acceptable method of birth
control, as determined by the PI.

- Willingness to participate in this study as evidenced by written informed consent.

Exclusion Criteria:

- Prior receipt of S. aureus rAT or rLukS-PV

- Known S. aureus infection requiring medical treatment within the 3 months prior to
investigational drug product injection

- Known active viral or bacterial infection

- Seropositivity for HIV infection

- Known or suspected abuse of prescribed or illicit drugs, or alcohol in the past year

- Use of any new medications (except oral contraceptives, over-the-counter medications,
or vitamin supplements) within the 7 days prior to investigational drug product
injection

- Use of investigational drugs, vaccines, or devices during the study or within the 30
days prior to each dose of investigational drug product injection, or anticipated use
of such items during the study

- Use of systemic steroids (any dose) or high daily dose inhaled steroids within the
last month. Use of low or medium daily dose inhaled, intranasal, or low potency
topical steroid creams/ointments is allowed unless such medication was begun within
the previous 7 days.

- History of a bleeding or coagulation disorder; or use of anti-coagulant medications
within 7 days prior to investigational product injection

- Actively breastfeeding

- Presence of grade I or higher abnormality in laboratory or vital signs parameter at
time of screening

- Presence of any condition which, in the opinion of the investigator, places the
subject at undue risk or potentially jeopardizes the quality of the data to be
generated