Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Research Article Immunology Virology

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

  • Text
  • PDF
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

×

Figure 6

A9E and G9E epitope-binding IgGs are widely represented in polyclonal plasma following natural ZIKV infection.

Options: View larger image (or click on image) Download as PowerPoint
A9E and G9E epitope-binding IgGs are widely represented in polyclonal pl...
(A) Blockade of binding (BOB) against A9E and G9E was tested among plasma at a 1:20 dilution from ZIKV and DENV cases from the UNC Traveler’s study, Nicaragua, and Sri Lanka, as was done for mAbs in Figure 4C. (B) The ZIKV cases were subdivided into primary (1°) and secondary (2°) ZIKV (ZIKV infection in a DENV-immune host). (C) Paired plasma specimens at 1:10 dilution from symptomatic ZIKV cases in Nicaragua were analyzed by BOB at early (day 21 after symptom onset) versus late (6 months after symptom onset) convalescence. An unpaired Student’s t test was performed to determine differences in means between groups as indicated by bars. **P < 0.01; ***P < 0.001; ****P < 0.0001. ns, not significant.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts