A Phase II Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults

Subjects will be randomized into one of 4 groups. One group will receive a placebo vaccine
and the others will receive one of 3 different dengue vaccine formations. Each subject will
receive two doses six months apart. Study subjects who elect to participate in a mosquito
transmissibility component of the study will undergo mosquito feedings during each of the two
assigned follow-up visits after vaccine dose 1. All subjects will have 11 venipunctures
during 11 visits (i.e., screening plus 10 study visits) over a period of nine months.

A third (booster) dose of post transfection F17 or F19 will be administered approximately 5
to 12 months after dose 2 to all subjects who received one of these formulation for their
first two doses. Volunteers will return for a single visit 6 months after receiving their
booster dose (long term follow-up)

Inclusion Criteria:

- A healthy male or female adult 18-45 years at the time of vaccination;

- Free of obvious health problems as established by medical history and physical
examination before entering into the study;

- Written informed consent obtained from the subject;

- Able to read the Subject Information Sheet and Consent Form;

- Subjects who the investigator believes can and will comply with the requirements of
the protocol (e.g., completion of the diary cards, return for follow-up visits) should
be enrolled in the study;

- If the subject is female, she must be of non-childbearing potential, i.e. either
surgically sterilized or one year post-menopausal; or, if of childbearing potential,
she must be abstinent or have used adequate contraceptive precautions (i.e.
intrauterine contraceptive device; oral contraceptives or other equivalent hormonal
contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable
contraceptives) for 30 days prior to vaccination, have a negative pregnancy test
within 48 hours prior to vaccination and must agree to continue such precautions for
60 days after completion of the vaccination series.

Exclusion Criteria:

- Pregnant or lactating female;

- Female planning to become pregnant or planning to discontinue abstinence or
contraceptive precautions;

- History of any neurological or behavioral disorder or seizures, with the exception of
a single febrile seizure in childhood;

- History of drug abuse or alcohol consumption (more than 2 drinks per day);

- History of allergic disease/reaction likely to be exacerbated by any component of the
vaccine;

- History of urticaria related to mosquito bites requiring medical attention;

- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal,
hematologic or endocrine functional defect, as determined by physical examination or
laboratory tests;

- Any confirmed or suspected immunosuppressive or immunodeficient condition;

- Subject seropositive for HBsAg, anti-HCV or anti-HIV;

- Acute disease at the time of enrollment (acute disease is defined as the presence of a
moderate or severe illness with or without fever);

- (Vaccine can be administered to persons with a minor illness such as diarrhea, mild
upper respiratory infection with or without low-grade febrile illness, i.e., oral
temperature <37.5°C/<99.5°F.)

- Chronic hepatomegaly, right upper quadrant abdominal pain or tenderness;

- Chronic splenomegaly, left upper quadrant abdominal pain or tenderness;

- Use of any investigational or non-registered drug or vaccine other than the study
vaccine within 30 days preceding the study vaccine (includes placebo) or planned use
during the study period;

- Planned administration of a vaccine not foreseen by the study protocol during the
period starting from 30 days before each dose of the study vaccine and ending 30 days
after;

- A planned move to a location that will prohibit participating in the trial for 9
months after the initial vaccination;

- Chronic administration (defined as more than 14 days) of immunosuppressants or other
immune-modifying drugs within 90 days preceding the first dose or planned
administration during the study period. For corticosteroids, this will mean
prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed;

- Administration of immunoglobulins and/or blood products within 90 days preceding the
first dose or planned administration during the study period;

- Any chronic systemic drug therapy to be continued during the study period (except for
vitamin/mineral supplements, a single anti-hypertension medication or routine
treatment for gastro-esophageal reflux).