INVESTIGATING THE ROLE OF DENGUE-SPECIFIC IMMUNITY IN PROTECTION AND DISEASE USING SYMPTOMATIC MOUSE MODELS

Abstract

Dengue virus (DENV), consisting of four distinct serotypes (DENV1-4), is a public health concern due its prevalence and severity. Development of therapeutics and vaccines has been hampered by a lack of understanding of disease pathogenesis and suitable animal models. Our laboratory has reported various symptomatic dengue mouse models that reproduced clinically relevant features. These mouse models recapitulate the phenomenon of antibody-dependent enhancement (ADE): mice born to DENV1-immune mothers developed enhanced disease upon DENV2 infection. Utilising these models, we investigated the role of dengue-specific immunity in dengue disease. Firstly, we investigated the relative contribution of maternal antibodies in disease outcome and identified breastfeeding as the major antibody transfer route. Next, we studied dengue-specific antibody populations present in our symptomatic models and demonstrated that antibodies specific to DENV structural proteins alone were capable of enhancing dengue disease. Lastly, we established that the pathogenic role of NS1 and NS1-mediated-immunity protection are DENV strain-dependent.