Mapping the diverse structural landscape of the flavivirus antibody repertoire

Flaviviruses are emerging arthropod-borne RNA viruses, causing a broad spectrum of life-threatening disease symptoms such as encephalitis and hemorrhagic fever. Successful vaccines exist against yellow fever virus, Japanese encephalitis virus and tick-borne encephalitis virus. However, vaccine development against other flaviviruses like dengue virus is not straightforward. This is partly because of the high sequence conservation and immunological cross-reactivity among flavivirus envelope glycoproteins leading to antibody mediated enhancement of disease. A comprehensive analyses of the structural landscape of humoral immune response against flaviviruses is crucial for antigen design. Here, we compare the available structural data of several flavivirus antibody complexes with a major focus on Zika virus and dengue virus and discuss the mapped epitopes, the stoichiometry of antibody binding and mechanisms of neutralization.