Evaluating the Safety and Protective Efficacy of a Single Dose of a Trivalent Live Attenuated Dengue Vaccine to Protect Against Infection With DENV-2

There are 4 types of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4), each capable of
causing dengue illness ranging from a mild illness to life-threatening disease. This study
will evaluate a trivalent live attenuated dengue admixture vaccine that contains 3 different
monovalent dengue vaccine candidates, representing 3 of the 4 dengue serotypes (DENV-1,
DENV-3, and DENV-4). Study researchers will evaluate the safety and protective efficacy of a
single dose of the trivalent dengue vaccine against viremia and rash induced by infection
with an attenuated DENV-2 virus (rDEN2Δ30-7169), administered 6 months after the trivalent
dengue vaccine.

This study will enroll healthy adults with no history of previous flavivirus infection. At
Day 0 (study entry), participants will be randomly assigned to receive either the trivalent
dengue vaccine admixture or placebo. On Day 180, all participants will receive the
rDEN2Δ30-7169 vaccine. Study visits will occur on Days 4, 6, 8, 10, 12, 14, 16, 21, 28, 56,
90, 150, 180, 184, 186, 188, 190, 192, 194, 196, 201, 208, 236, 270, and 360. Visits will
include physical examinations and blood collection. All participants will record their
temperature 3 times a day for 16 days after each vaccination.

Inclusion Criteria:

- Adult male or female between 18 and 50 years of age, inclusive

- 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-second
vaccination

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

- Females Only: Female participants of childbearing potential willing to use effective
contraception. Reliable methods of contraception include: hormonal birth control,
condoms with spermicide, diaphragm with spermicide, surgical sterilization,
intrauterine device, abstinence (6 months or longer since last sexual encounter). All
female participants will be considered having child-bearing potential except for
those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to
vaccination), or post-menopausal status documented as at least 1 year since last
menstrual period.

Exclusion Criteria:

- Females Only: Currently pregnant, as determined by positive beta-human
choriogonadotropin (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, 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

- Screening laboratory values of Grade 1 or above for absolute neutrophil (ANC),
alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol

- Any 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 that 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), by HBV 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 of 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

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

- Refusal to allow storage of specimen for future research

Inclusion Criteria for Second Vaccine:

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

- Available for the duration of the study, approximately 26 weeks after the second dose

- Females Only: Female participants of childbearing potential willing to use effective
contraception. Reliable methods of contraception include: hormonal birth control,
condoms with spermicide, diaphragm with spermicide, surgical sterilization,
intrauterine device, abstinence (6 months or longer since last sexual encounter). All
female participants will be considered having child-bearing potential except for
those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to
vaccination), or post-menopausal status documented as at least 1 year since last
menstrual period.

Exclusion Criteria for Second Vaccine:

- Anaphylaxis or angioedema following the first dose of vaccine

- Females only: Currently pregnant, as determined by positive beta-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, 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

- Any condition that in the opinion of the investigator would jeopardize the safety or
rights of a participant to understand and cooperate with the requirements of the
study protocol

- Any significant alcohol or drug abuse in the past 12 months that 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

- HCV infection, by screening and confirmatory assays

- HBV infection, by 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 inoculation. 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 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

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

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

- Refusal to allow storage of specimens for future research

Other Treatment and Ongoing Exclusion Criteria:

The following criteria will be reviewed on Study Days 28 and 56 following each
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.

- 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 any 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