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 language | English (US) |
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Pages (from-to) | 1422-1433.e4 |
Journal | Cell Reports |
Volume | 27 |
Issue number | 5 |
DOIs | |
State | Published - Apr 30 2019 |
Keywords
- HIV incidence
- antibody biomarker
- antibody profiling
- antibody response to HIV
- immunodominant HIV epitopes
- serosignature
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology