A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants
Condition: Dengue
MeSH terms: Dengue
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The main target populations for the tetravalent live attenuated dengue virus vaccine are
      indigenous populations, especially infants less than 2 years old, residing in areas of the
      world endemic for dengue and at risk of developing dengue hemorrhagic fever (DHF). The
      presence of maternal dengue antibody during the first year of life makes it unlikely that a
      vaccine given during that time will have long-term efficacy, as the vaccine virus would
      likely be neutralized prior to necessary replication. Children older than 18 months may have
      preexisting flavivirus antibody. Therefore, vaccination of infants living in Thailand early
      in the second year of life (between the ages of 12 and 18 months) seems most beneficial. The
      aim of this trial is to evaluate the safety and immunogenicity of a two-dose schedule of a
      tetravalent live attenuated dengue vaccine in flavivirus antibody naïve infants beginning at
      12-15 months of age.

        -  To assess the kinetics of dengue neutralizing antibodies to each dengue virus serotype
           one and four years following dose 2 of dengue/control vaccination in the setting of
           potential wild-type dengue virus exposure.

        -  To assess the immunogenicity, the safety and reactogenicity of a booster dose of dengue
           vaccine administered at Year 3 following primary vaccination.
    

Detailed description: 
      -  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?
    

Intervention name(s): Tetravalent live attenuated dengue vaccine; Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine
Intervention type(s): Biological; Biological
Intervention description(s): DEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection.
Infants received 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 control vaccines are licensed for use in Thailand.
All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection.
A booster dose of DEN vaccine was given to all subjects previously vaccinated with DEN vaccine in Dengue -001. The booster dose was administered approximately 42 months after dose 2 (at the Year 3 visit).; Infants received 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 control vaccines are licensed for use in Thailand.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Prevention
Keywords: Dengue, Vaccine, Thailand