Biography
Biography: Gavin R Screaton
Abstract
Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. Of these approximately one quarter are clinically apparent or symptomatic. The majority of these result in a self-limited, but none the less unpleasant febrile illness, dengue fever. 1-5% of infections lead to a more severe disease, dengue haemorrhagic fever, which is characterized by a severe vascular leak, hypovolaemia and in extreme cases shock and haemorrhage. Dengue exists as four highly divergent serotypes differing in sequence by some 30-35%; infection with one serotype does not provide protection against the other three. In endemic areas serotypes frequently co-circulate and repeat infections are common. Interestingly, severe disease is much more common in secondary as opposed to primary infections, implying a role of the acquired immune system in disease pathogenesis. Understanding this immune enhancement of disease is crucial for the design of safe and effective vaccines. Through clinical collaborations in Thailand and Vietnam, we have been studying the immune response to dengue in cohorts of infected children. We have characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE) that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. We will describe the antibody response to the two virion surface glycoproteins prM and E and discuss the E dimer epitope (EDE), a novel site bridging the 90 basic head to tail envelope dimers making up the virion surface. The antibodies directed to the EDE are both potent and broadly neutralizing across the dengue serocomplex suggesting the EDE could be a target for a new generation of subunit vaccines against dengue.