Experimental Dengue Virus Challenge of Human Subjects Previously Vaccinated with Live-Attenuated Tetravalent Dengue Virus Vaccines.

Department of Virus Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910.
The Journal of Infectious Diseases (Impact Factor: 5.85). 12/2012; DOI: 10.1093/infdis/jis744
Source: PubMed

ABSTRACT Background. Protection against dengue requires immunity against all 4 serotypes of virus. 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 dengue naïve control subjects were inoculated subcutaneously (s.c.)with either 10(3) pfu's of Dengue-1 (DENV-1) or 10(5) pfu's of Dengue-3 (DENV-3) challenge viruses. Two additional subjects who did not develop DENV-3 neutralizing antibody (Nab) from TDV were re-vaccinated with 10(4) pfu's 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 enzymes, 2 had values greater than 10 times 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 though one subject was protected despite lack of measurable Nab at the time of DENV-1 challenge.Conclusions. Vaccination with live-attenuated TDV induced variable protection against s.c. challenge. DENV-3 experimental challenge was associated with transient but significant hepatitis.

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