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Comprehensive Profiling of HIV Antibody Evolution

2019; Cell Press; Volume: 27; Issue: 5 Linguagem: Inglês

10.1016/j.celrep.2019.03.097

2639-1856

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

Monoclonal and Polyclonal Antibodies Research

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.