Alonso Sylvie
National University of Singapore, Singapore
Title: Murine models of dengue and their utility for drug and vaccine testing
Biography
Biography: Alonso Sylvie
Abstract
Dengue (DEN), the most serious arthropod-borne viral disease, manifests as a mild febrile illness to life-threatening hemorrhage and vascular leakage. The development of an animal model has long been recognized as a major roadblock in understanding dengue pathogenesis and validating therapeutic and prophylactic strategies prior to clinical stages. Humans and mosquitoes are the natural hosts for dengue virus (DENV) in its urban cycle. While most immunocompetent mice are not susceptible to infection from all four DENV serotypes, type I & II interferon deficient mice may develop asymptomatic transient viremia and in few cases, relevant clinical manifestations. Furthermore, it is possible to reproduce the antibody-dependent enhancement of disease severity (ADE) in this mouse model. In this conference, we will present the various mouse models of dengue currently available in our laboratory, ranging from asymptomatic transient viremia to lethal models associated with vascular leakage or liver damage, two relevant clinical manifestations. We will also present our unique models of ADE mediated by maternal antibodies acquired during both gestation and breastfeeding. This mouse models platform has made our group visible to the Dengue research scene, and has attracted a significant number of collaborations, licensing and research service contracts with both industry partners and public institutions for evaluating the in vivo efficacy of prophylactic and therapeutic candidates.