Live-attenuated Tetravalent Dengue Vaccine in Dengue-naïve Children, Adolescents, and Adults in Mexico City: Randomized Controlled Phase 1 Trial of Safety and Immunogenicity

Pediatr Infect Dis J. 2011 Jan;30(1):e9-17. doi: 10.1097/INF.0b013e3181fe05af.

Abstract

Background: Preliminary results in healthy, young US adults showed that a tetravalent, live-attenuated dengue vaccine (TDV) was safe and immunogenic, but no data are available in children.

Methods: In a multicenter, randomized, controlled, observer-blinded study in the city of Mexico, children aged 2 to 5, 6 to 11, and 12 to 17 years (36 children per age group), and adults (n = 18) aged <45 years received the following: 3 injections of TDV at months 0, 3.5, and 12 (TDV-TDV-TDV), or 1 injection of yellow fever vaccine (YF) at month 0, and 2 injections of TDV at months 3.5 and 12 (YF-TDV-TDV). Adverse events and biologic safety (biochemistry and hematology) were documented. Plaque reduction neutralization test (PRNT50) antibody titers against the TDV parental viruses were measured 28 days after vaccination. Seropositivity was defined as antibody titers ≥10 1/dil.

Results: No vaccine-related serious adverse events, other significant clinical adverse events, or clinically significant trends in biologic safety were observed. Reactogenicity did not increase with successive TDV injections, and mild-to-moderate injection site pain, headache, myalgia, and malaise were most commonly reported (14%-40% after each vaccination). After 3 TDV vaccinations, the seropositivity rate against each dengue serotype was in the range 77% to 92%, compared with 85% to 94% after completion of the YF-TDV-TDV regimen. Of the 2- to 11-year-old participants, 95% were seropositive against ≥3 serotypes after 3 vaccinations.

Conclusions: A 3-dose TDV regimen had a favorable safety profile in children and adults and elicited neutralizing antibody responses against all 4 serotypes. These findings support the continued development of this vaccine.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Dengue / immunology
  • Dengue / prevention & control*
  • Dengue Vaccines / administration & dosage
  • Dengue Vaccines / adverse effects*
  • Dengue Vaccines / immunology*
  • Female
  • Humans
  • Male
  • Mexico
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects*
  • Vaccines, Attenuated / immunology*
  • Viremia
  • Yellow Fever Vaccine / administration & dosage
  • Young Adult

Substances

  • Dengue Vaccines
  • Vaccines, Attenuated
  • Yellow Fever Vaccine