Infection with Dengue viruses (DENV) has become a major public health problem in the tropics and an emerging threat for the United States. There are 4 serotypes of this virus that cause diseases ranging widely in severity, from self-limited dengue fever (DF) to potentially fatal dengue hemorrhagic fever-dengue shock syndrome (DHF/DSS). Currently, no licensed vaccine is available to prevent DENV infections. Thus, the main goal of our laboratory is to develop an effective tetravalent DENV vaccine. Toward this effort, we have developed expression vectors encoding prM/env genes of all four DENV serotypes. Several of these vectors have been tested as vaccine candidates in mice and one vaccine candidate was also evaluated in non-human primates. We are currently evaluating vaccine candidates against DENV-1 and DENV-3. We also attempt to identify biomarkers for the early detection of patients at risk of developing DHF.

Upon the introduction of West Nile virus (WNV) in the Americas and the Caribbean, we initiated a pilot study to test if prior immunity to DENV can protect Balb/c mice against morbidity and mortality induced by West Nile virus (WNV) infection. If cross-protection is achieved, this project will allow us to determine the type and duration of the immune responses that may correlate with protection, which is important to improve the design of broad spectrum vaccines that could potentially protect against both pathogens, DENV and WNV.

Research Support:

• RCMI pilot project G12RR03051, 08/01/06-07/31/08, Characterization of the immune response and outcome of sequential flavivirus infections in the mouse mode
• R21 AI055814-01, 08-01-2003 to 07-31-2006, Evaluation Studies of a Dengue-2 DNA Vaccine in Monkeys
• MBRS-SCORE S06-GM008224, 09-01-00 to 07-31-04, Evaluation Studies of a Dengue-2 Envelope DNA Vaccine
• Center for Clinical Research, UPR-Medical Sciences Campus, 01/15/04 to 07/31/05, Identification of biomakers for early stages of the Dengue infection
• Internal Caribbean Primate Research Center funding