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Development of a potent and protective germline-like antibody lineage against Zika virus in a convalescent human

By Fei Gao, Xiaohe Lin, Linling He, Ruoke Wang, Han Wang, Xuanling Shi, Fuchun Zhang, Chibiao Yin, Linqi Zhang, Jiang Zhu, Lei Yu

Posted 05 Jun 2019
bioRxiv DOI: 10.1101/661918 (published DOI: 10.3389/fimmu.2019.02424)

Zika virus (ZIKV) specific neutralizing antibodies hold a great promise for antibody-based interventions and vaccine design against ZIKV infection. However, their development in infected patients remain unknown. Here, we report on the dynamic development of a potent and protective ZIKV-specific human antibody ZK2B10 initially isolated from a ZIKV convalescent individual using next-generation sequencing (NGS). The unbiased repertoire analysis showed dramatic changes in many families of heavy and light chain variable regions. However, lineage tracing of ZK2B10 revealed limited somatic hypermutation throughout the 12 months since the onset of symptom. In particular, NGS-derived germline-like somatic variants neutralized and protected mice from lethal challenge of ZIKV without detectable cross-reactivity with Dengue virus (DENV). Site-directed mutagenesis identified two residues within ? chain, N31 and S91 that are essential to the functional maturation. 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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