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了HIV-1感染中公共抗体克隆型的存在

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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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