Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch

Antibody-dependent enhancement (ADE) is an important safety concern for vaccine development against dengue virus (DENV) and its antigenically related Zika (ZIKV) because may prime deleterious antibodies to enhance natural infections. Cross-reactive targeting the conserved fusion loop epitope (FLE) are known as main sources of ADE. We design ZIKV immunogens engineered change FLE conformation but preserve neutralizing epitopes. Single vaccination conferred sterilizing immunity without ADE DENV-serotype 1–4 infections abrogated maternal–neonatal transmission in mice. Unlike wild-type-based inducing predominately cross-reactive ADE-prone antibodies, B cell profiling revealed that vaccines switched immunodominance dispersed patterns DENV enhancement. The crystal structure immunogen showed dimeric envelope protein with disruption. provide candidates will prevent both infection infection-/vaccination-induced (ZIKV). Gao colleagues designed a induced fetal protection mice challenged did not induce following subsequent infection.