Experimental dengue virus challenge of human subjects previously vaccinated with live attenuated tetravalent dengue vaccines

Wellington Sun*, Kenneth H. Eckels, J. Robert Putnak, Arthur G. Lyons, Stephen J. Thomas, David W. Vaughn, Robert V. Gibbons, Stefan Fernandez, Vicky J. Gunther, Mammen P. Mammen, John D. Statler, Bruce L. Innis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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 103 plaque-forming units (PFU) of DENV-1 or 105 PFU of DENV-3. Two additional subjects who did not develop DENV-3 neutralizing antibody (NAb) from TDV were revaccinated with 104 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.

Original languageEnglish
Pages (from-to)700-708
Number of pages9
JournalJournal of Infectious Diseases
Issue number5
StatePublished - 1 Mar 2013
Externally publishedYes


  • dengue
  • live virus challenge
  • tetravalent vaccine


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