Comprehensive Profiling of HIV Antibody Evolution

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

doi:10.1016/j.celrep.2019.03.097

Comprehensive Profiling of HIV Antibody Evolution

Cell Rep. 2019 Apr 30;27(5):1422-1433.e4. doi: 10.1016/j.celrep.2019.03.097.

Authors

Susan H Eshleman¹, Oliver Laeyendecker², Kai Kammers³, Athena Chen⁴, Mariya V Sivay⁵, Sanjay Kottapalli⁵, Brandon M Sie⁵, Tiezheng Yuan⁵, Daniel R Monaco⁵, Divya Mohan⁵, Daniel Wansley⁵, Tomasz Kula⁶, Charles Morrison⁷, Stephen J Elledge⁶, Ron Brookmeyer⁸, Ingo Ruczinski⁴, H Benjamin Larman⁹

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: seshlem@jhmi.edu.
² Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Division of Biostatistics and Bioinformatics, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁵ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA.
⁷ FHI 360, Clinical and Epidemiologic Sciences, Durham, NC, USA.
⁸ Department of Biostatistics, University of California at Los Angeles, Los Angeles, CA, USA.
⁹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: hlarman1@jhmi.edu.

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.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-HIV Agents / therapeutic use
Antibody Specificity*
CD4-Positive T-Lymphocytes / immunology
Epitopes / immunology
Female
HIV Antibodies / immunology*
HIV Antigens / immunology
HIV Seropositivity / drug therapy
HIV Seropositivity / immunology*
Humans

Substances

Anti-HIV Agents
Epitopes
HIV Antibodies
HIV Antigens

Abstract

Publication types

MeSH terms

Substances

Grants and funding