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 glyco-protein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are sero-logically 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 antige-nicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

Keywords:

DENGUE VIRUS

MONOCLONAL-ANTIBODIES

DEPENDENT ENHANCEMENT

CROSS-REACTIVITY

HIGH-THROUGHPUT

VACCINE

POTENT

DETERMINANTS

INFECTION

RESPONSES

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Abstract

AI Summary

Journal

Organization