Michael Verdolin Rose Hills
Proportion & Potency of Fusion Loop Antibodies in Dengue Infection
The four dengue virus serotypes (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern worldwide, responsible for over 100 million infections yearly, of whom 51 million will develop symptoms ranging from self-limiting dengue fever to fatal dengue shock syndrome. Infection generates antibodies (Abs) that can cross-react with another serotype, increasing the risk of subsequent symptomatic or severe DENV infection. Previous studies aiming at determining the Ab repertoire against DENV implicate the envelope protein’s fusion loop (FL) as an immunodominant epitope Anti-FL Abs are broadly cross-reactive but poorly neutralizing. In vitro studies have shown that anti-FL Abs potently induce antibody-dependent enhancement (ADE), but it has yet to be demonstrated in vivo. My project focuses on developing and using the molecular tools necessary to measure the proportion of anti-FL Abs in human serum collected 6 to 12 months before a secondary infection and determine whether a high level of anti-FL Abs is associated with disease protection or enhancement.