title: Experimental dengue virus challenge of human subjects previously vaccinated with live attenuated tetravalent dengue vaccines.
abstract: BACKGROUND
  Protection against dengue requires immunity against all 4 serotypes of dengue virus (DENV). Experimental challenge may be useful in evaluating vaccine-induced immunity.
  
  
  METHODS
  Ten subjects previously vaccinated with a live attenuated tetravalent dengue vaccine (TDV) and 4 DENV-naive control subjects were challenged by subcutaneous inoculation of either 10(3) plaque-forming units (PFU) of DENV-1 or 10(5) PFU of DENV-3. Two additional subjects who did not develop DENV-3 neutralizing antibody (NAb) from TDV were revaccinated with 10(4) PFU of live attenuated DENV-3 vaccine to evaluate memory response.
  
  
  RESULTS
  All 5 TDV recipients were protected against DENV-1 challenge. Of the 5 TDV recipients challenged with DENV-3, 2 were protected. All DENV-3-challenge subjects who developed viremia also developed elevated liver enzyme levels, and 2 had values that were >10 times greater than normal. Of the 2 subjects revaccinated with DENV-3 vaccine, 1 showed a secondary response to DENV-2, while neither showed such response to DENV-3. All 4 control subjects developed dengue fever from challenge. Protection was associated with presence of NAb, although 1 subject was protected despite a lack of measurable NAb at the time of DENV-1 challenge.
  
  
  CONCLUSIONS
  Vaccination with TDV induced variable protection against subcutaneous challenge. DENV-3 experimental challenge was associated with transient but marked elevations of transaminases.
authors.affiliation: Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. wellington.sun@fda.hhs.gov
authors.forename: Wellington
authors.initials: W
authors.lastname: Sun
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Eckels
authors.forename: J Robert
authors.initials: JR
authors.lastname: Putnak
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Lyons
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gibbons
authors.forename: Stefan
authors.initials: S
authors.lastname: Fernandez
authors.forename: Vicky J
authors.initials: VJ
authors.lastname: Gunther
authors.forename: Mammen P
authors.initials: MP
authors.lastname: Mammen
authors.forename: John D
authors.initials: JD
authors.lastname: Statler
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
mesh_terms: D000328:Adult; D001774:Blood Chemical Analysis; D003715:Dengue / Q000473:pathology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014766:Viremia / Q000473:pathology / Q000517:prevention & control; D055815:Young Adult
chemical_list: D053059:Dengue Vaccines; D014613:Vaccines, Attenuated