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Author Notes:

M. J. Mulligan, Division of Infectious Diseases, Hope Clinic of the Emory Vaccine Center, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA (mark.mulligan@emory.edu).

Emory Zika Patient Study Team: Briyana Domjahn, MPH, Dongli Wang, BS, Mary Bower, RN, Rijalda Deovic, BS, Sree Aramgam, BS, Sara Jo Johnson, BS, Dean Kleinhenz, BS, JoAnn Sadowski, BS, Talib Sirajud-Deen, BA, and Jesse Waggoner, MD

See publication for full list of acknowledgements.

H. W. has received grant support from Takeda Vaccines, outside the submitted work.

All other authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Subjects:

Research Funding:

This work was supported by the Emory University School of Medicine; Emory Vaccine Center; Georgia Research Alliance; and the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID; contract HHSN272201300018I) and by a supplemental award to NIH/NIAID/DMID (grant AI115651).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Infectious Diseases
  • Microbiology
  • Zika
  • immunity
  • pregnancy
  • viral persistence
  • flavivirus
  • DENGUE VIRUS-INFECTION
  • PROLONGED DETECTION
  • WHOLE-BLOOD
  • VACCINE
  • ACTIVATION
  • IMMUNITY
  • DISEASE
  • EBOLA

Innate, T-, and B-Cell Responses in Acute Human Zika Patients

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Journal Title:

Clinical Infectious Diseases

Volume:

Volume 66, Number 1

Publisher:

, Pages 1-+

Type of Work:

Article | Final Publisher PDF

Abstract:

There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. Methods. In 5 returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Results. Two pregnant, flavivirus-experienced patients had viral RNA persist in plasma for > 44 and > 26 days. Three days after symptom onset, transient increases in proinflammatory monocytes began followed at 5 days by transient decreases in myeloid dendritic cells. Anti-Zika virus immunoglobulin M was detected at day 7 after symptom onset, persisted beyond 103 days, and remained equivocal through day 172. Zika virus-specific plasmablasts and neutralizing antibodies developed quickly; dengue virus-specific plasmablasts and neutralizing antibodies at high titers developed only in flavivirus-experienced patients. Zika virus-and dengue virus-specific memory B cells developed in both flavivirus-naive and-experienced patients. CD4+ T cells were moderately activated and produced antiviral cytokines after stimulation with Zika virus C, prM, E, and NS5 peptides in 4/4 patients. In contrast, CD8+ T cells were massively activated, but virus-specific cells that produced cytokines were present in only 2/4 patients assessed. Conclusions. Acute infections with Zika virus modulated antigen-presenting cell populations early. Flavivirus-experienced patients quickly recalled cross-reactive MBCs to secrete antibodies. Dengue virus-naive patients made little dengue-specific antibody but developed MBCs that cross-reacted against dengue virus. Zika virus-specific functional CD4+ T cells were readily detected, but few CD8+ T cells specific for the tested peptides were found.

Copyright information:

© The Author(s) 2017.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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