India is now an epicenter of dengue with an estimated 20-40 million infections per year making India the country with the largest number of dengue infections in the world. This ICIDR program is designed with a focus on dengue virus infection in India. The overall objectives are twofold: (i) To build capacity for dengue research i India using state of the art tools and technologies; and (ii) To address critical scientific questins important to the health and well being of dengue exposed population in India. The following Specific Aims are proposed: 1) To use a systems biological approach to define molecular signatures of the innate and adaptive immune responses that occur following acute dengue infection and to determine the extent to which such signatures correlate with disease outcome. 2) To determine whether IgG Fc glycan composition is a determinant of antibody-dependent enhancement of secondary dengue virus infection and whether Fc glycan composition may have a role in the pathogenesis of severe dengue disease. 3) To characterize the human B cell response during dengue infection and generate dengue virus specific monoclonal antibodies from plasmablasts. 4) To characterize CD4 and CD8 T cell responses in dengue patients. 5) To define dengue virus genotypes in context of disease severity and immune response induced in dengue patients. Taken together the above studies should provide insight into the pathogenesis of dengue virus infection in India and provide guidelines for diagnostics and treatment of dengue infection. Our ICIDR program is designed in such a way that the state of the art tools and technologies needed for all the aspects of the proposed research are set up in India and actually used there to carry the proposed research. This model allows scientific training, enhanced collaborative interactions, and sustained capacity building in India.
India brings the highest dengue disease burden in the world, but, unfortunately, it remains the weakest link in the fight against the dengue menace. Many questions beg answers with reference to human immunity to dengue- an understanding of which is critical for making better vaccines, diagnostics and biomarkers.
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