Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.

Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development. [Display omitted] • Using whole ZIKV as a probe, we identify potent ZIKV-specific neutralizing antibodies • Neutralizing mAbs target four distinct epitopes at the E dimer-dimer interface • The four ZIKV-specific epitopes are prevalent in ZIKV infection in humans • mAbs from all four antigenic groups provide protection against ZIKV infection Sankhala et al. use Zika virus as a bait to identify potent neutralizing monoclonal antibodies (mAbs) that are highly specific to Zika virus. These mAbs bind conformational epitopes across the virion dimer-dimer interface and provide protection against infection in a mouse Zika virus challenge model. [ABSTRACT FROM AUTHOR]