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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02424

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

 Fei Gao1,  Xiaohe Lin2, Linling He2, Ruoke Wang1,  Wang Han1, Xuanling Shi1, Fuchun Zhang3, Chibiao Yin3, Linqi Zhang1*,  Jiang Zhu2* and  Lei Yu4*
  • 1School of Medicine, Tsinghua University, China
  • 2The Scripps Research Institute, United States
  • 3Guangzhou Medical University, China
  • 4Guangzhou 8th People’s Hospital, China

Zika virus (ZIKV) specific neutralizing antibodies hold great promise for antibody-based interventions and vaccine design against ZIKV infection. However, their development in infected patients remains unclear. Here, we applied next-generation sequencing (NGS) to probe the dynamic development of a potent and protective ZIKV E DIII-specific antibody ZK2B10 isolated from a ZIKV convalescent individual. The unbiased repertoire analysis showed dramatic changes in the usage of antibody variable region germline genes. However, lineage tracing of ZK2B10 revealed limited somatic hypermutation and transient expansion during the twelve months following the onset of symptoms. The NGS-derived, germline-like ZK2B10 somatic variants neutralized ZIKV potently and protected mice from lethal challenge of ZIKV without detectable cross-reactivity with Dengue virus (DENV). Site-directed mutagenesis identified two residues within the  chain, N31 and S91, that are essential to the functional maturation of ZK2B10. The repertoire and lineage features unveiled here will help elucidate the developmental process and protective potential of E DIII-directed antibodies against ZIKV infection

Keywords: Zika virus infection, Guillain–Barré syndrome, Microcephaly, neutralizing antibody, Antibody repertoire, Next-generation sequencing

Received: 14 Jun 2019; Accepted: 27 Sep 2019.

Copyright: © 2019 Gao, Lin, He, Wang, Han, Shi, Zhang, Yin, Zhang, Zhu and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Linqi Zhang, School of Medicine, Tsinghua University, Beijing, 100084, Beijing Municipality, China,
Prof. Jiang Zhu, The Scripps Research Institute, La Jolla, 92037, California, United States,
Prof. Lei Yu, Guangzhou 8th People’s Hospital, Guangzhou, China,