Modeling dengue immune responses mediated by antibodies: insight on the immunopathogenesis of severe disease

Dengue fever is a viral mosquito-borne infection, a major international public health concern. With four antigenically related but distinct viruses (DENV-1 to DENV-4), the occurrence of the virus as four distinct serotypes results in many complications in disease response. Infection with one serotype results in lifelong protective immunity. Additionally, antibodies generated by exposure to any one type cross-react with other types, providing short duration cross protective immunity. Subsequent infection by a different dengue serotype increases the risk of developing severe disease with a high fatality rate. This disease augmentation phenomenon is called antibody-dependent enhancement (ADE).Here we present a minimalistic mathematical model developed to describe the dengue immunological response mediated by antibodies. Based on body cells and free virus interactions resulting infected cells activating antibody production, we explore the feature of ADE when pre-existing antibodies, analyzing: i) primary dengue infection, ii) secondary dengue infection with the same virus and iii) secondary dengue infection with a different dengue virus. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature and this framework will now be refined to be validated with the available laboratory data.