Safety and Immunogenicity of Various Formulations of Live Attenuated Tetravalent Dengue Vaccine in Healthy US Adults
Safety and Immunogenicity of Various Formulations of Live Attenuated Tetravalent Dengue Vaccine in Healthy US Adults
This descriptive study will evaluate the safety and immunogenicity of 3 different
 formulations of the WRAIR dengue vaccine compared to a placebo.
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).