Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor

Abstract

The isolation and characterization of monoclonal broadly neutralizing antibodies (nAbs) from natural HIV-1-infected individuals play very important roles in understanding nAb responses to HIV-1 infection and designing vaccines and therapeutics. Many broadly nAbs have been isolated from individuals infected with HIV-1 clade A, B, C, etc., but, as an important recombinant virus, the identification of broadly nAbs in CRF01_AE-infected individuals remains elusive. In this study, we used antigen-specific single B-cell sorting and monoclonal antibody expression to isolate monoclonal antibodies from a CRF01_AE-infected Chinese donor (GX2016EU04), a broad neutralizer based on neutralizing activity against a cross-clade virus panel. We identified a series of HIV-1 monoclonal cross-reactive nAbs, termed F2, H6, BF8, F4, F8, BE7, and F6. F6 could neutralize 21 of 37 tested HIV-1 Env-pseudotyped viruses (57%) with a geometric mean value of 12.15 μg/ml. Heavy and light chains of F6 were derived from IGHV4-34 and IGKV 2-28 germlines, complementarity determining region (CDR) 3 loops were composed of 18 and 9 amino acids, and somatic hypermutations (SHMs) were 16.14% and 11.83% divergent from their respective germline genes. F6 was a GP120-specific nAb and recognized the linear epitope. We identified for the first time a novel broadly HIV-1-neutralizing antibody, termed F6, from a CRF01_AE-infected donor, which could enrich the research of HIV-1 nAbs and provide useful insights for designing vaccine immunogens and antibody-based therapeutics.

Acknowledgements

This work was supported by the National Postdoctoral Program for Innovative Talents (BX201600078 to Bin Ju), the National Natural Science Foundation of China (81861138011 to Yiming Shao; 81571991 to Min Wei; 31600734 to Dan Li), European Research Infrastructures for Poverty Related Diseases (312661 to Yiming Shao), and SKLID Development Grants (2016SKLID307 to Min Wei; 2016SKLID602 to Yiming Shao). We thank Dr. Zhiyong Shen at the Guangxi Center for Disease Control and Prevention for collecting the PBMC samples. We are grateful to The Scripps Research Institute for providing TriMut, TriMut/368/370/474, HIV-2_7312A, and HIV-2_7312A-C1. We also appreciate the generous gifts of RSC3, ΔRSC3, and full-length IgG1 heavy and light chain expression vectors from the Vaccine Research Center, National Institute of Allergy and Infectious Disease.

Author contributions

Bin Ju, Min Wei, and Yiming Shao conceived and designed the study; Bin Ju, Dan Li, Li Ren, Jiali Hou, Yanling Hao, Hua Liang, and Shuo Wang performed the experiments and analyzed the data; Jiang Zhu designed and purified the sorting probe BG505; and Bin Ju, Min Wei, and Yiming Shao wrote and revised the paper.

Conflict of interest

The authors declare that they have no conflict of interest.

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