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Delineating antibody recognition against Zika virus during natural infection
Lei Yu, … , Fuchun Zhang, Linqi Zhang
Lei Yu, … , Fuchun Zhang, Linqi Zhang
Published June 15, 2017
Citation Information: JCI Insight. 2017;2(12):e93042. https://doi.org/10.1172/jci.insight.93042.
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Research Article Immunology Infectious disease

Delineating antibody recognition against Zika virus during natural infection

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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.

Authors

Lei Yu, Ruoke Wang, Fei Gao, Min Li, Jianying Liu, Jian Wang, Wenxin Hong, Lingzhai Zhao, Yingfen Wen, Chibiao Yin, Hua Wang, Qi Zhang, Yangyang Li, Panpan Zhou, Rudian Zhang, Yang Liu, Xiaoping Tang, Yongjun Guan, Cheng-Feng Qin, Ling Chen, Xuanling Shi, Xia Jin, Gong Cheng, Fuchun Zhang, Linqi Zhang

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Figure 1

Binding and neutralizing activity of sequential plasma samples from 2 ZIKV-infected individuals during natural infection.

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Binding and neutralizing activity of sequential plasma samples from 2 ZI...
Serial dilutions of plasma samples were analyzed for their binding (A) to E glycoprotein of ZIKV (GZ01, KU820898), DENV1 (GZ35, KP723476), and DENV2 (GZ05, KP012546) by ELISA and for neutralizing activity (B) against ZIKV (GZ01), DENV1 (Hawaii strain), and DENV2 (New Guinea strain) by plaque assay. All results were derived from at least 2 independent experiments.

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