Comprehensive Profiling of HIV Antibody Evolution

Abstract

Summary: 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. Keywords: antibody response to HIV, antibody profiling, HIV incidence, antibody biomarker, serosignature, immunodominant HIV epitopes