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J Infect Dis. 2013 Mar 1;207(5):700-8. doi: 10.1093/infdis/jis744. Epub 2012 Dec 5.

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

Author information

1
Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. wellington.sun@fda.hhs.gov

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.

PMID:
23225894
DOI:
10.1093/infdis/jis744
[Indexed for MEDLINE]

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