rDEN2/4Delta30(ME), a live attenuated chimeric dengue serotype 2 vaccine is safe and highly immunogenic in healthy dengue-naïve adults

Hum Vaccin. Nov-Dec 2006;2(6):255-60. doi: 10.4161/hv.2.6.3494. Epub 2006 Nov 5.

Abstract

rDEN2/4Delta30(ME) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 candidate vaccine rDEN4Delta30 have been replaced by those of the prototypic DEN2 NGC virus. rDEN2/4Delta30(ME) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-naïve adult volunteers. Eight volunteers received placebo. Volunteers were monitored closely for adverse events and serum was collected for determination of the level and duration of viremia and neutralizing antibody response. The vaccine was well tolerated by all volunteers. The most common adverse events observed were a transient asymptomatic rash and mild neutropenia. All vaccines seroconverted to DEN2 and maintained significant antibody titers throughout the six-month trial duration. Eleven vaccinees had vaccine virus recovered from the blood during the study. RNA derived from virus isolates obtained from viremic volunteers was sequenced for confirmation of retention of the Delta30 mutation in the 3' UTR. The Delta30 mutation remained unchanged in each isolate, confirming the stability of the Delta30 mutation. Further evaluation of this vaccine in a tetravalent formulation is warranted.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Base Sequence
  • Dengue / prevention & control*
  • Dengue Vaccines* / administration & dosage
  • Dengue Vaccines* / adverse effects
  • Dengue Vaccines* / genetics
  • Dengue Vaccines* / immunology
  • Dengue Virus / classification
  • Dengue Virus / genetics
  • Dengue Virus / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Recombinant Proteins* / genetics
  • Recombinant Proteins* / immunology
  • Recombinant Proteins* / metabolism
  • Treatment Outcome
  • Vaccines, Attenuated* / administration & dosage
  • Vaccines, Attenuated* / adverse effects
  • Vaccines, Attenuated* / genetics
  • Vaccines, Attenuated* / immunology
  • Viral Proteins* / genetics
  • Viral Proteins* / immunology
  • Viral Proteins* / metabolism

Substances

  • Antibodies, Viral
  • Dengue Vaccines
  • Recombinant Proteins
  • Vaccines, Attenuated
  • Viral Proteins