Delineating antibody recognition against Zika virus during natural infection
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
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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Research Article Immunology Infectious disease

Delineating antibody recognition against Zika virus during natural infection

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 4

Summary of isolated mAbs and phylogenetic analysis.

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Summary of isolated mAbs and phylogenetic analysis. (A) Antibodies were ...
(A) Antibodies were listed accordingly to the sampling time points from the patients together with the type of B cells originally derived from, P for plasmablast and M for memory. Epitope specificity was determined by staining with DI/II– and DIII–expressing yeast clones from ZIKV, DENV1 and DENV2. IC50 represents the half-maximal inhibitory concentrations in the plaque neutralization assay, whereas EC50 represents the half-maximal effective concentrations in ELISA binding assay, and both of which are presented in heatmap format for differential activities. Only the CDR3 regions of heavy and light variable chain are shown together with their family names and percent similarity with the corresponding germline ancestor sequence. (B) Unrooted neighbor-joining tree depicting the relationship of isolated mAbs; left panel for the heavy chain and right panel for the light chain variable region. The branch length is drawn to scale so that the relatedness between different amino acid sequences can be readily assessed. Individual sequences are named at the tip of the branches, and their epitope specificity and neutralizing potency are indicated as in the heatmap.