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Human antibody response to Zika targets type-specific quaternary structure epitopes
Matthew H. Collins, … , Sean A. Diehl, Aravinda M. de Silva
Matthew H. Collins, … , Sean A. Diehl, Aravinda M. de Silva
Published April 18, 2019
Citation Information: JCI Insight. 2019;4(8):e124588. https://doi.org/10.1172/jci.insight.124588.
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Research Article Immunology Virology

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

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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.

Authors

Matthew H. Collins, Huy A. Tu, Ciara Gimblet-Ochieng, Guei-Jiun Alice Liou, Ramesh S. Jadi, Stefan W. Metz, Ashlie Thomas, Benjamin D. McElvany, Edgar Davidson, Benjamin J. Doranz, Yaoska Reyes, Natalie M. Bowman, Sylvia Becker-Dreps, Filemón Bucardo, Helen M. Lazear, Sean A. Diehl, Aravinda M. de Silva

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Figure 1

Primary serologic response to ZIKV.

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Primary serologic response to ZIKV.
(A) Plasma from 4 primary ZIKV cases...
(A) Plasma from 4 primary ZIKV cases (DT168, DT172, DT206, and DT244) were tested for IgG binding to ZIKV (top) and DENV (bottom) over the dilution series indicated on the x axis. (B) Primary ZIKV plasma and primary (DT001) and secondary (DT000) DENV plasma were tested for IgG binding to ZIKV recombinant E (ZIKV E80), DENV recombinant E (DENV E80), ZVEDI, and ZVEDIII. (C) Neutralization assays were also performed for each primary ZIKV plasma as well as a secondary (2°) DENV control. NHS, naive human plasma (negative binding control for ELISA).

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