Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study

J Infect Dis. 2016 May 15;213(10):1562-72. doi: 10.1093/infdis/jiv762. Epub 2015 Dec 23.

Abstract

Background: A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries.

Methods: This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4.

Results: Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups.

Conclusions: TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure.

Keywords: adults; children; immunogenicity; live attenuated tetravalent dengue vaccine; safety.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Child
  • Child, Preschool
  • Colombia
  • Dengue / immunology
  • Dengue / prevention & control*
  • Dengue Vaccines / administration & dosage
  • Dengue Vaccines / immunology*
  • Dengue Vaccines / standards
  • Dengue Virus / immunology*
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Puerto Rico
  • Safety
  • Singapore
  • Thailand
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vaccines, Attenuated / standards
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated