Evaluating the Safety and Immune Response to a Dengue Virus Vaccine in Healthy Adults

Dengue viruses can cause dengue fever and the more severe disease, dengue hemorrhagic
fever/shock syndrome (DHF/DSS). Infection with dengue viruses is the leading cause of
hospitalization and death in children in at least 8 tropical Asian countries. There are 4
types of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4), each of which can cause dengue
illness ranging from a mild illness to life-threatening disease. This study will evaluate
the experimental rDEN2Δ30-7169 vaccine for the prevention of illness due to DENV-2. The
purpose of this study is to evaluate the safety and immunogenicity of this vaccine in
healthy adults with no history of previous flavivirus infection.

At study entry, participants will be randomly assigned to receive either the dengue virus
vaccine or placebo. They will remain in the clinic for 30 minutes after receiving the
injection for monitoring. Study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21,
28, 56, and 180. All study visits will include a blood collection, and most study visits
will include a physical examination. Female participants will have a pregnancy test at
select visits. Participants will record their temperature at least 3 times a day for the
first 16 days; study researchers will review these readings during the study visits.

Inclusion Criteria:

- Good general health as determined by physical examination, laboratory screening, and
review of medical history

- Available for the duration of the study, approximately 26 weeks post vaccination

- Willingness to participate in the study as evidenced by signing the informed consent
document

- Female participants of childbearing potential willing to use effective contraception
for the duration of the trial. More information on this criterion can be found in the
protocol.

Exclusion Criteria:

- Currently pregnant, as determined by positive beta-human chorionic gonadotropin (HCG)
test, or breastfeeding

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
rheumatologic, autoimmune, or renal disease by history, physical examination, and/or
laboratory studies

- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
affects the ability of the participant to understand and cooperate with the
requirements of the study protocol

- Confirmed screening laboratory values of Grade 1 or above for absolute neutrophil
count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the
protocol. Confirmation will be obtained by repeating the test to ensure the abnormal
value was not due to aberrancy.

- Any other condition that in the opinion of the investigator would jeopardize the
safety or rights of a participant in the trial or would render the participant unable
to comply with the protocol

- Any significant alcohol or drug abuse in the past 12 months which has caused medical,
occupational, or family problems, as indicated by participant history

- History of a severe allergic reaction or anaphylaxis

- Severe asthma (emergency room visit or hospitalization within the last 6 months)

- HIV infection, by screening and confirmatory assays

- Hepatitis C virus (HCV) infection, by screening and confirmatory assays

- Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening

- Any known immunodeficiency syndrome

- Use of anticoagulant medications

- Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within
28 days prior to or following vaccination. Immunosuppressive dose of corticosteroids
is defined as greater than or equal to 10 mg prednisone equivalent per day for
greater than or equal to 14 days.

- Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior
to vaccination or anticipated receipt of any vaccine during the 28 days following
vaccination

- Asplenia

- Receipt of blood products within the past 6 months, including transfusions or
immunoglobulin or anticipated receipt of any blood products or immunoglobulin during
the 28 days following vaccination

- History or serologic evidence of previous dengue virus infection or other flavivirus
infection (e.g., yellow fever virus, St. Louis encephalitis virus, West Nile virus)

- Previous receipt of a flavivirus vaccine (licensed or experimental)

- Anticipated receipt of any investigational agent in the 28 days before or after
vaccination

- Has definite plans to travel to a dengue endemic area during the study

- Refusal to allow storage of specimens for future research

Other Treatments and Ongoing Exclusion Criteria:

The following criteria will be reviewed on Days 28 and 56 following vaccination. If any
become applicable during the study, the participant will not be included in further
immunogenicity evaluations, as of the exclusionary visit. The participant will, however,
be encouraged to remain in the study for safety evaluations for the duration of the study.

Ongoing Exclusion Criteria:

- Use of any investigational drug or investigational vaccine other than the study
vaccine during the 28-day period post vaccination

- Chronic administration (greater than or equal to 14 days) of steroids (defined as
prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants,
or other immune-modifying drugs initiated during the 28-day period post vaccination
(topical and nasal steroids are allowed)

- Receipt of a licensed vaccine during the 28-day period post vaccination

- Receipt of immunoglobulins and/or any blood products during the 28-day period post
vaccination

- Pregnancy