Experimental Dengue Virus Challenge of Human Subjects Previously Vaccinated With Live Attenuated Tetravalent Dengue 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: 5.78). 12/2012; 207(5). 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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