Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7. doi: 10.1073/pnas.1607931113. Epub 2016 Jun 27.

Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus.

Author information

1
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;
2
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;
3
Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
4
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
5
The Hope Clinic of the Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322;
6
Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
7
Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, Department of Medicine, University of Chicago, Chicago, IL 60637.
8
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; jwramme@emory.edu rahmed@emory.edu.
9
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322; jwramme@emory.edu rahmed@emory.edu.

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.

KEYWORDS:

B-cell responses; Zika virus; antibodies; cross-reactivity

PMID:
27354515
PMCID:
PMC4948328
DOI:
10.1073/pnas.1607931113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center