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JCI Insight. 2017 Jun 15;2(12). pii: 93042. doi: 10.1172/jci.insight.93042. [Epub ahead of print]

Delineating antibody recognition against Zika virus during natural infection.

Author information

1
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
2
Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
3
Viral Disease and Vaccine Translational Research Unit, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
4
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
5
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
6
State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
7
Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Abstract

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that shares a considerable degree of homology with dengue virus (DENV). Here, we examined longitudinal antibody response against ZIKV during natural infection in 2 convalescent individuals. By decomposing the antibody recognition into DI/DII and DIII of the E glycoprotein, we showed their development in humans followed a spatiotemporal hierarchy. Plasma binding to DI/DII appeared to peak and wane during early infection with extensive cross-reactivity with DI/DII of DENV. Binding to DIII, however, peaked early but persisted months into the infection without detectable cross-reactivity with DIII of DENV. A clear trend of increase in DIII-specific neutralizing activity was observed over the course of infection. mAbs isolated during early infection are largely DI/DII specific, weakly neutralizing, and highly cross-reactive with DENV, while those from later infection are more diverse in recognition, potently neutralizing, and ZIKV specific. The most potent neutralizing mAb targeting the DIII provided 100% protection in mice from lethal ZIKV infection and could therefore serve as a promising candidate for antibody-based therapy and prevention. The dynamic features unveiled here will assist us to better understand the pathogenesis of ZIKV infection and inform rational design of vaccines.

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