Multi-Donor Longitudinal Antibody Repertoire Sequencing Reveals the Existence of Public Antibody Clonotypes in HIV-1 Infection

多供体纵向抗体库测序揭示 HIV-1 感染中存在公共抗体克隆型

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作者:Ian Setliff, Wyatt J McDonnell, Nagarajan Raju, Robin G Bombardi, Amyn A Murji, Cathrine Scheepers, Rutendo Ziki, Charissa Mynhardt, Bryan E Shepherd, Alusha A Mamchak, Nigel Garrett, Salim Abdool Karim, Simon A Mallal, James E Crowe Jr, Lynn Morris, Ivelin S Georgiev

Abstract

Characterization of single antibody lineages within infected individuals has provided insights into the development of Env-specific antibodies. However, a systems-level understanding of the humoral response against HIV-1 is limited. Here, we interrogated the antibody repertoires of multiple HIV-infected donors from an infection-naive state through acute and chronic infection using next-generation sequencing. This analysis revealed the existence of "public" antibody clonotypes that were shared among multiple HIV-infected individuals. The HIV-1 reactivity for representative antibodies from an identified public clonotype shared by three donors was confirmed. Furthermore, a meta-analysis of publicly available antibody repertoire sequencing datasets revealed antibodies with high sequence identity to known HIV-reactive antibodies, even in repertoires that were reported to be HIV naive. The discovery of public antibody clonotypes in HIV-infected individuals represents an avenue of significant potential for better understanding antibody responses to HIV-1 infection, as well as for clonotype-specific vaccine development.

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