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

• Published in: Cell host & microbe Vol. 23; no. 6; pp. 845 - 854.e6
• Main Authors: Setliff, Ian, McDonnell, Wyatt J., Raju, Nagarajan, Bombardi, Robin G., Murji, Amyn A., Scheepers, Cathrine, Ziki, Rutendo, Mynhardt, Charissa, Shepherd, Bryan E., Mamchak, Alusha A., Garrett, Nigel, Karim, Salim Abdool, Mallal, Simon A., Crowe, James E., Morris, Lynn, Georgiev, Ivelin S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.06.2018; Cell Press
• Subjects: antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - genetics; Antibodies, Neutralizing - immunology; Antibody Formation - immunology; antibody repertoire; B cells; computational biology; HIV Antibodies - blood; HIV Antibodies - chemistry; HIV Antibodies - genetics; HIV Antibodies - immunology; HIV Infections - blood; HIV Infections - immunology; HIV-1; HIV-1 - immunology; Humans; Immunity, Humoral - immunology; immunology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Longitudinal Studies; next-generation sequencing; public antibodies; RNA - blood; RNA - immunology; Sequence Analysis, Protein; Sequence Analysis, RNA; Single-Cell Analysis; systems immunology; HIV-1; computational biology; public antibodies; next-generation sequencing; antibodies; B cells; systems immunology; immunology; antibody repertoire
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2018.05.001

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. [Display omitted] •Within-donor longitudinal antibody repertoire to HIV-1 infection was analyzed by NGS•Public antibody clonotypes shared among multiple HIV-infected individuals were uncovered•A public antibody clonotype shared by three donors was confirmed to be HIV reactive•Antibody sequences from HIV-naive repertoires are similar to known HIV antibodies The overall antibody repertoires of HIV-infected subjects are considered to be unique. Setliff et al. analyze the longitudinal antibody repertoire of HIV-1-infected individuals to uncover the existence of “public” HIV-reactive antibodies in multiple subjects. Antibody sequences with high identity to known HIV-reactive antibodies were identified even in HIV-naive repertoires.