Leading researchers from Imperial College London and the University of Melbourne have identified a new class of potent antibodies that effectively neutralise all four viruses known to cause dengue. The study, published in Nature Immunology, has important implications for the development of a universal dengue vaccine.
Dengue is classed as the most important mosquito-borne viral disease in the world by the World Health Organisation (WHO). More than one third of the world’s population are at risk of infection, with an estimated 50 million infections occurring annually across 100 different countries. In most cases dengue causes flu-like symptoms and joint pain, but in severe cases can develop into dengue haemorrhagic fever, which can be fatal. Infection is caused by one of the four antigenically related, but genetically distinct, dengue viruses. Currently there are no effective treatments or approved vaccines available for dengue. However, we may be closer to a dengue vaccine than we think, as scientists from Imperial College London and the University of Melbourne have recently discovered a new class of human antibodies capable of neutralising all four strains of dengue virus.
The study was led by Professor Gavin Screaton and Dr Juthathip Mongkolsapaya from Imperial College London, in collaboration with Dr Felix Rey and colleagues from the Institut Pasteur in Paris. Professor Screaton and colleagues generated human monoclonal antibodies (mAbs) from plasmablasts (antibody-producing cells) isolated from the blood of Vietnamese patients who had been hospitalised with dengue. They then screened a panel of 145 mAbs and identified a new class of highly potent antibodies which target a previously unknown epitope (a specific region which antibodies can bind to in order to elicit an immune response) which they named the ‘envelope dimer epitope’ (EDE). The EDE is described as a ‘molecular bridge’ that joins two envelope protein subunits on the surface of dengue virus.
What is unique about this new class of antibodies is their ability to neutralise all four of the dengue-causing viruses, as the EDE is highly conserved across all dengue virus strains. The authors tested these antibodies on dengue viruses produced by infected mosquito cells and infected human cells, and reported that the mAbs were capable of fully neutralising virus produced by both of these cell types.
The discovery of this highly potent, broadly reactive and new class of antibodies paves the way for a new vaccine strategy for dengue, and raises hopes of the possibility of a single universal dengue vaccine conferring protection against all four strains of the virus.