rDEN2/4Δ30(ME), a live attenuated chimeric dengue serotype 2 vaccine, is safe and highly immunogenic in healthy dengue-naïve adults

Anna P. Durbin, Julie H. McArthur, Jennifer A. Marron, Joseph E. Blaney, Bhavin Thumar, Kimberli Wanionek, Brian R. Murphy, Stephen S. Whitehead

Research output: Contribution to journalArticlepeer-review

Abstract

rDEN2/4Δ30(ME) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 candidate vaccine rDEN4Δ30 have been replaced by those of the prototypic DEN2 NGC virus. rDEN2/4Δ30(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 vaccinees 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 Δ30 mutation in the 3′ UTR. The Δ30 mutation remained unchanged in each isolate, confirming the stability of the Δ30 mutation. Further evaluation of this vaccine in a tetravalent formulation is warranted.

Original languageEnglish (US)
Pages (from-to)255-260
Number of pages6
JournalHuman vaccines
Volume2
Issue number6
DOIs
StatePublished - 2006

Keywords

  • DEN2
  • Human trial
  • Live attenuated chimeric dengue vaccine

ASJC Scopus subject areas

  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)

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