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

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.

Conditions

• Dengue

Interventions

BIOLOGICAL

Tetravalent live attenuated dengue vaccine

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).

BIOLOGICAL

Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine

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.

Sponsors & Collaborators

• GlaxoSmithKline

  collaborator INDUSTRY

• U.S. Army Medical Research and Development Command

  lead FED

Principal Investigators

• Robert V. Gibbons, MD · U.S. Army Medical Component Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS)

• Veerachai Watanaveeradej, MD · Infectious Disease Department of Pediatrics Phramongkutklao Hospital

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

12 Months

Max Age

15 Months

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2004-02-29

Primary Completion

2009-06-30

Completion

2009-06-30

Countries

• Thailand

Study Locations