Development of a Potent and Protective Germline-Like Antibody Lineage Against Zika Virus in a Convalescent Human

Frontiers in Immunology

Ruoke Wang¹  Fei Gao¹  Linqi Zhang¹  Xuanling Shi¹  Han Wang¹  Xiaohe Lin²  Jiang Zhu²  Linling He²  Chibiao Yin³  Lei Yu³  Fuchun Zhang³ 

[1] Department of Basic Medical Sciences, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China;Department of Integrative Structural and Computational Biology, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States;Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China;

关键词: Zika virus infection;    Guillain–Barré syndrome;    microcephaly;    neutralizing antibody;    antibody repertoire;    next-generation sequencing;   

DOI  :  10.3389/fimmu.2019.02424

来源: DOAJ

【 摘 要 】

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 12 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 λ 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.

【 授权许可】

Unknown