Increasing the flavivirus envelope glycoprotein dimer stability to elicit potent and broadly neutralising antibody responses

Dengue is a mosquito-borne virus infection of the tropics and subtropics. About  400 million infections occur annually of which one quarter lead to overt illness. About 1-5% of infections are severe and can lead to the condition dengue haemorrhagic fever with dramatic fluid loss and bleeding which is life threatening. Dengue frequently occurs as an epidemic and puts huge pressures on the healthcare systems in affected countries. A recent large-scale trial of an anti-dengue vaccine gave some protection, but this was below that expected and although the vaccine has been licensed it cannot be used in children under the age of nine meaning that further development of dengue vaccines will be required. Through our work on dengue immune responses in infected people we have identified a key group of antibodies which can potently neutralise dengue infection. We have recently demonstrated that these same antibodies can also neutralise Zika virus.

Defining the site where these antibodies bind onto the dengue and Zika viruses will point the way to a novel dengue vaccine design. We have assembled a team of researchers to further the design and testing of this new dengue/Zika vaccine approach.