Human antibody response to Zika targets type-specific quaternary structure epitopes

• Type of Material: Article
• Authors: Matthew Collins, Emory University; Huy A. Tu, University of Vermont; Ciara Gimblet-Ochieng, University of North Carolina; Guei-Jiun Alice Liou, University of North Carolina; Ramesh S. Jadi, University of North Carolina; Stefan W. Metz, University of North Carolina; Ashlie Thomas, University of North Carolina; Benjamin D. McElvany, University of Vermont; Edgar Davidson, Integral Molecular Inc.; Benjamin J. Doranz, Integral Molecular Inc.; Yaoska Reyes, National Autonomous University of Leon; Natalie M. Bowman, University of North Carolina; Sylvia Becker-Dreps, University of North Carolina; Filemon Bucardo, National Autonomous University of Leon; Helen M. Lazear, University of North Carolina; Sean A. Diehl, University of Vermont; Aravinda M. de Silva, University of North Carolina
• Language: English
• Date: 2019-04-18
• Publisher: The American Society of Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2019 American Society for Clinical Investigation
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.124588
• Title of Journal or Parent Work: JCI insight
• Volume: 4
• Issue: 8
• Grant/Funding Information: NIH contract HHSN272201400058C to BJD supported epitope mapping.; Zika-TS cohort in León, Nicaragua was supported with grant R21AI129532 to SBD and FB.; Sequencing work was performed by the Vermont Integrated Genomics Resource and supported by P30GM118228.; Mouse experiments supported by start-up funds to HML from the UNC Lineberger Comprehensive Cancer Center.; This study was supported by R01AI107731 (to AdS) and CDC BAA 2017-N-18041 (to AdS) and T32AI055402 (HT).; At the University of Vermont, cell sorting was performed by UVM-COM Flow Cytometry and Cell Sorting Facility (with thanks to Roxana del Rio-Guerra, PhD) and supported by S10-ODO18175 and P30 GM118228).
• Keywords: Science & Technology; DEPENDENT ENHANCEMENT; B-CELL RESPONSES; Life Sciences & Biomedicine; Research & Experimental Medicine; YELLOW-FEVER; CROSS-REACTIVITY; HUMAN NEUTRALIZING ANTIBODIES; DISEASE ENHANCEMENT; TICK-BORNE ENCEPHALITIS; PROTECTION; MONOCLONAL-ANTIBODIES; Medicine, Research & Experimental; DENGUE VIRUS
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

The recent Zika virus (ZIKV) epidemic in the Americas has revealed rare but serious manifestations of infection. ZIKV has emerged in regions endemic for dengue virus (DENV), a closely related mosquito-borne flavivirus. Cross-reactive antibodies confound studies of ZIKV epidemiology and pathogenesis. The immune responses to ZIKV may be different in people, depending on their DENV immune status. Here, we focus on the human B cell and antibody response to ZIKV as a primary flavivirus infection to define the properties of neutralizing and protective antibodies generated in the absence of preexisting immunity to DENV. The plasma antibody and memory B cell response is highly ZIKV type-specific, and ZIKV-neutralizing antibodies mainly target quaternary structure epitopes on the viral envelope. To map viral epitopes targeted by protective antibodies, we isolated 2 type-specific monoclonal antibodies (mAbs) from a ZIKV case. Both mAbs were strongly neutralizing in vitro and protective in vivo. The mAbs recognize distinct epitopes centered on domains I and II of the envelope protein. We also demonstrate that the epitopes of these mAbs define antigenic regions commonly targeted by plasma antibodies in individuals from endemic and nonendemic regions who have recovered from ZIKV infections.