The immune response to dengue virus infection is a well-coordinated balancing act. New research shows that an imbalanced response — driven partially by the productive infection of antigen-presenting cells — is associated with progression to severe disease.
More than half of the global population is at risk of infection with any of the four co-circulating serotypes of dengue virus (DENV1 to DENV4). Although 75% of DENV infections are asymptomatic, around 96 million people develop dengue fever and require clinical interventions annually, and up to 5% of these are severe cases1. A universally effective vaccine has proved elusive. Post-marketing studies of the first licensed vaccine against dengue (Dengvaxia, from Sanofi Pasteur) reported that it increased the risk of severe disease in dengue-seronegative people, and this finding negatively affected vaccine confidence2,3. A better understanding of the factors that underlie severe dengue progression could have helped to prevent this vaccine rollout and will support the rational design of future vaccines and therapeutics. In this issue