Too much or too little—better than some Dengue fever is caused by a mosquito-transmitted flavivirus resembling Zika virus. Both viruses can cause severe diseases in humans with catastrophic sequelae. It has been suspected in humans, and shown in animal models, that the host's immune responses can make disease worse. Katzelnick et al. examined data from a long-term study of Nicaraguan children exposed to dengue virus (see the Perspective by Feinberg and Ahmed). They confirmed that antibody-dependent enhancement of disease occurs at a specific range of antibody concentrations. Low levels of antibody did not enhance disease, intermediate levels exacerbated disease, and high antibody titers protected against severe disease. These findings have major implications for vaccines against flaviviruses. Indeed, recent vaccine trials have shown evidence of severe disease in some recipients who were previously exposed to virus. Science , this issue p. 929 ; see also p. 865

Antibody-dependent enhancement of severe dengue disease in humans