Primary Outcome Measures:
- Occurrence of any, and grade 3 solicited adverse events (AEs) within 21 days follow-up after dose 1 of study vaccine;
- N antibody (GMT) to DEN serotypes 1, 2, 3 and 4, 30 and 90 days after the last study vaccine dose
Secondary Outcome Measures:
- Safety endpoints
- Occurrence of any, and grade 3 solicited adverse events (AEs) within 21 days follow-up after dose 2 of study vaccine;
- Occurrence of each type of any and grade 3 solicited AE within the 21-day solicited follow-up period after each dose;
- Occurrence of unsolicited AEs within 31 days (days 0-30) after any study vaccine dose;
- Occurrence of serious adverse events (SAEs) throughout the entire study period;
- Occurrence of alert values for safety laboratory determinations within 31 days after each vaccine dose.
- Occurrence of abnormal findings at DEN physical examination after each vaccine dose
- Occurrence of suspected and confirmed dengue throughout the entire study period
- Immunogenicity endpoints
- N antibody titer above the assay cut-off, to each DEN serotype, after each dose;
- N antibody titer above the assay cut-off, to all dengue serotypes after each dose;
- N sero-response to each DEN serotype after each dose
- N antibody titer to each DEN serotype after vaccine dose 1
- Occurrence of measurable dengue viremia at specified time points following each vaccine dose.
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)