A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults: a randomized, double-blind clinical trial

J Infect Dis. 2013 Mar 15;207(6):957-65. doi: 10.1093/infdis/jis936. Epub 2013 Jan 17.

Abstract

Background: Dengue virus (DENV) causes hundreds of millions of infections annually. Four dengue serotypes exist, and previous infection with one serotype increases the likelihood of severe disease with a second, heterotypic DENV infection.

Methods: In a randomized, placebo-controlled study, the safety and immunogenicity of 4 different admixtures of a live attenuated tetravalent (LATV) dengue vaccine were evaluated in 113 flavivirus-naive adults. Serum neutralizing antibody levels to all 4 dengue viruses were measured on days 0, 28, 42, and 180.

Results: A single dose of each LATV admixture induced a trivalent or better neutralizing antibody response in 75%-90% of vaccinees. There was no significant difference in the incidence of adverse events between vaccinees and placebo-recipients other than rash. A trivalent or better response correlated with rash and with non-black race (P < .0001). Black race was significantly associated with a reduced incidence of vaccine viremia.

Conclusions: TV003 induced a trivalent or greater antibody response in 90% of flavivirus-naive vaccinees and is a promising candidate for the prevention of dengue. Race was identified as a factor influencing the infectivity of the LATV viruses, reflecting observations of the effect of race on disease severity in natural dengue infection.

Trial registration: ClinicalTrials.gov NCT01072786.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • African Continental Ancestry Group
  • American Native Continental Ancestry Group
  • Antibodies, Viral / blood*
  • Dengue / prevention & control
  • Dengue Vaccines / administration & dosage
  • Dengue Vaccines / adverse effects*
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology*
  • Double-Blind Method
  • European Continental Ancestry Group
  • Exanthema / virology
  • Female
  • Humans
  • Male
  • Oceanic Ancestry Group
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Viremia / virology
  • Young Adult

Substances

  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated

Associated data

  • ClinicalTrials.gov/NCT01072786