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Innate, T-, and B-Cell Responses in Acute Human Zika Patients
- Source :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
- Publication Year :
- 2017
-
Abstract
- Understanding the immune response during acute Zika in humans will aid vaccine design and testing. In 5 acute patients, including 2 pregnant women, viral levels and innate, T-, and B-cell responses against Zika or dengue viruses are described.<br />Background 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.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Adult
Male
Time Factors
viruses
Dengue virus
Adaptive Immunity
medicine.disease_cause
Antibodies, Viral
Virus
Zika virus
Dengue fever
viral persistence
03 medical and health sciences
0302 clinical medicine
Immune system
Zika
flavivirus
Pregnancy
T-Lymphocyte Subsets
medicine
Humans
030212 general & internal medicine
Articles and Commentaries
B cell
B-Lymphocytes
biology
business.industry
Zika Virus Infection
Zika Virus
Viral Load
biology.organism_classification
medicine.disease
Virology
Antibodies, Neutralizing
immunity
Immunity, Innate
3. Good health
Flavivirus
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Immunoglobulin M
biology.protein
RNA, Viral
Female
business
Subjects
Details
- ISSN :
- 15376591
- Volume :
- 66
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Accession number :
- edsair.doi.dedup.....47482367528187e1ae84030f47ab29ea