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Author Notes:

E-mail: mricciardi@med.miami.edu

See publication for full list of author contributions.

We would like to thank our human study subjects for their time and contributions as well as the University of Miami Flow Cytometry Core facility for their assistance in sorting and analysis of the plasmablasts.

We appreciate The Clinical and Translational Research Site at the University of Miami Hospital and thank the clinical team there for their flexibility and assistance in all collections.

We also thank Lauren Harte, Josh Chemtob, Peter Cole, Refugio Robles-Sikisaka, and Glenn Oliveira for their technical assistance and support.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This work was supported by a grant from the U.S. National Institutes of Health supplement to 1PO1AI094420-05 awarded to D.I.W., and an internal grant from the University of Miami Clinical Translational Research Institute (CTSI) [http://www.miamictsi.org].

Additional support was provided by the U.S. National Institutes for Health grants HHSN27220140045C, 1PO1AI106695-01A1, U19AI118626-01, and the EU-grant 734584 to A.S.

The views expressed are those of the authors and not necessarily those of the funding bodies.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Infectious Diseases
  • Parasitology
  • Tropical Medicine
  • CROSS-REACTIVITY
  • MAXIMUM-LIKELIHOOD
  • STRUCTURAL BASIS
  • UNITED-STATES
  • SEQUENCE DATA
  • ANTIBODY
  • ENHANCEMENT
  • NEUTRALIZATION
  • TRANSMISSION
  • REPLICATION

Ontogeny of the B- and T-cell response in a primary Zika virus infection of a dengue-naive individual during the 2016 outbreak in Miami, FL

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Journal Title:

PLoS Neglected Tropical Diseases

Volume:

Volume 11, Number 12

Publisher:

, Pages e0006000-e0006000

Type of Work:

Article | Final Publisher PDF

Abstract:

Zika virus (ZIKV) is a mosquito-borne flavivirus of significant public health concern. In the summer of 2016, ZIKV was first detected in the contiguous United States. Here we present one of the first cases of a locally acquired ZIKV infection in a dengue-naïve individual. We collected blood from a female with a maculopapular rash at day (D) 5 and D7 post onset of symptoms (POS) and we continued weekly blood draws out to D148 POS. To establish the ontogeny of the immune response against ZIKV, lymphocytes and plasma were analyzed in a longitudinal fashion. The plasmablast response peaked at D7 POS (19.6% of CD19 + B-cells) and was undetectable by D15 POS. ZIKV-specific IgM was present at D5 POS, peaked between D15 and D21 POS, and subsequently decreased. The ZIKV-specific IgG response, however, was not detected until D15 POS and continued to increase after that. Interestingly, even though the patient had never been infected with dengue virus (DENV), cross-reactive IgM and IgG binding against each of the four DENV serotypes could be detected. The highest plasma neutralization activity against ZIKV peaked between D15 and D21 POS, and even though DENV binding antibodies were present in the plasma of the patient, there was neither neutralization nor antibody dependent enhancement (ADE) of DENV. Interestingly, ADE against ZIKV arose at D48 POS and continued until the end of the study. CD4 + and CD8 + T-cells recognized ZIKV-NS2A and ZIKV-E, respectively. The tetramer positive CD8 + T-cell response peaked at D21 POS with elevated levels persisting for months. In summary, this is the first study to establish the timing of the ontogeny of the immune response against ZIKV.

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© 2017 Public Library of Science. All Rights Reserved.

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

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