Comprehensive Profiling of HIV Antibody Evolution

• Main Authors: Susan H. Eshleman, Oliver Laeyendecker, Kai Kammers, Athena Chen, Mariya V. Sivay, Sanjay Kottapalli, Brandon M. Sie, Tiezheng Yuan, Daniel R. Monaco, Divya Mohan, Daniel Wansley, Tomasz Kula, Charles Morrison, Stephen J. Elledge, Ron Brookmeyer, Ingo Ruczinski, H. Benjamin Larman
• Format: Article
• Language: English
• Published: Elsevier 2019-04-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S221112471930436X

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