Comprehensive Profiling of HIV Antibody Evolution

Susan H. Eshleman, Oliver Laeyendecker, Kai Kammers, Athena Chen, Mariya Sivay, Sanjay Kottapalli, Brandon M. Sie, Tiezheng Yuan, Daniel R. Monaco, Divya Mohan, Daniel Wansley, Tomasz Kula, Charles Morrison, Stephen J. Elledge, Ronald Brookmeyer, Ingo Ruczinski, H. Benjamin Larman

Research output: Contribution to journalArticle

Abstract

This study evaluates HIV antibody responses and their evolution during the course of HIV infection. A phage display system is used to characterize antibody binding to >3,300 HIV peptides in 57 adults with early- to late-stage infection. We find that the number of unique epitopes targeted (“antibody breadth”) increases early in infection and then stabilizes or declines. A decline in antibody breadth 9 months to 2 years after infection is associated with subsequent antiretroviral treatment (ART) initiation, and a faster decline in antibody breadth is associated with a shorter time to ART initiation. We identify 266 peptides with increasing antibody reactivity over time and 43 peptides with decreasing reactivity over time. These data are used to design a prototype four-peptide “serosignature” to predict duration of HIV infection. We also demonstrate that epitope engineering can be used to optimize peptide binding properties for applications such as cross-sectional HIV incidence estimation. Eshleman et al. quantify antibody binding to >3,300 HIV peptides from early- to late-stage infection using a phage display system (VirScan). Binding diversity (breadth) reaches individual-specific set points; breadth decline is associated with CD4 cell loss. Time-dependent binding specificities are identified, optimized, and used to predict duration of HIV infection.

Original languageEnglish (US)
Pages (from-to)1422-1433.e4
JournalCell Reports
Volume27
Issue number5
DOIs
StatePublished - Apr 30 2019

Keywords

  • antibody biomarker
  • antibody profiling
  • antibody response to HIV
  • HIV incidence
  • immunodominant HIV epitopes
  • serosignature

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Eshleman, S. H., Laeyendecker, O., Kammers, K., Chen, A., Sivay, M., Kottapalli, S., Sie, B. M., Yuan, T., Monaco, D. R., Mohan, D., Wansley, D., Kula, T., Morrison, C., Elledge, S. J., Brookmeyer, R., Ruczinski, I., & Larman, H. B. (2019). Comprehensive Profiling of HIV Antibody Evolution. Cell Reports, 27(5), 1422-1433.e4. https://doi.org/10.1016/j.celrep.2019.03.097