A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants

* This is a Phase I/II, randomized, observer-blind, controlled trial. Thirty-four flavivirus naïve infants will be randomized to the vaccine group and 17 infants to the control group. * Infants receive dengue vaccine at study months 0 and 6 or control vaccine (Varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both are licensed for use in Thailand. * All infants subsequently receive an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. * Infants are monitored daily for 21 days following each dengue or control vaccination and 7 days after each JE vaccination for solicited adverse events. Unsolicited events will be recorded up to 31 days (days 0-30) after dengue/control vaccinations and each day after dose 1 of JE vaccine until the concluding study visit. * Study duration (excluding screening) is approximately 8.5 months for each subject. * Each enrollee is followed a four year period following dose 2 of dengue/control vaccination to assess for dengue-related hospitalizations and dengue antibody kinetics. * Investigators will administer a 3rd dose of tetravalent dengue vaccine to all subjects who received 2 doses of dengue vaccine (0 and 6 months) during the primary phase of the study. The 3rd dose will be administered 3 years following the primary vaccination series. Peripheral blood mononuclear cells (PBMCs) and sera will be collected at the time of dose 3, and twice again at one month and one year following dose 3 from dengue group subjects.

Investigators will address the following questions:

1. Is a 3rd dose of live virus tetravalent dengue vaccine safe in Thai toddlers/children? 2. Is a 3rd dose of live virus tetravalent dengue vaccine required in toddlers/children to induce optimal immune (neutralizing antibody, cellular mediated immunity) responses? 3. Is there evidence of T and B cell memory following a primary dengue vaccination series (dose 1 and 2)? 4. How does a 3rd dose of live virus tetravalent dengue vaccine impact B and T cell memory?