Cell Reports (Feb 2023)
Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor
- Kelsey A. Pilewski,
- Steven Wall,
- Simone I. Richardson,
- Nelia P. Manamela,
- Kaitlyn Clark,
- Tandile Hermanus,
- Elad Binshtein,
- Rohit Venkat,
- Giuseppe A. Sautto,
- Kevin J. Kramer,
- Andrea R. Shiakolas,
- Ian Setliff,
- Jordan Salas,
- Rutendo E. Mapengo,
- Naveen Suryadevara,
- John R. Brannon,
- Connor J. Beebout,
- Rob Parks,
- Nagarajan Raju,
- Nicole Frumento,
- Lauren M. Walker,
- Emilee Friedman Fechter,
- Juliana S. Qin,
- Amyn A. Murji,
- Katarzyna Janowska,
- Bhishem Thakur,
- Jared Lindenberger,
- Aaron J. May,
- Xiao Huang,
- Salam Sammour,
- Priyamvada Acharya,
- Robert H. Carnahan,
- Ted M. Ross,
- Barton F. Haynes,
- Maria Hadjifrangiskou,
- James E. Crowe, Jr.,
- Justin R. Bailey,
- Spyros Kalams,
- Lynn Morris,
- Ivelin S. Georgiev
Affiliations
- Kelsey A. Pilewski
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Steven Wall
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Simone I. Richardson
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
- Nelia P. Manamela
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa
- Kaitlyn Clark
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Tandile Hermanus
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa
- Elad Binshtein
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Rohit Venkat
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Giuseppe A. Sautto
- Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA
- Kevin J. Kramer
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Andrea R. Shiakolas
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Ian Setliff
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Jordan Salas
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Rutendo E. Mapengo
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa
- Naveen Suryadevara
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- John R. Brannon
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Connor J. Beebout
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Rob Parks
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Nagarajan Raju
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Nicole Frumento
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Lauren M. Walker
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Emilee Friedman Fechter
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Juliana S. Qin
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Amyn A. Murji
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Katarzyna Janowska
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Bhishem Thakur
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Jared Lindenberger
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Aaron J. May
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Xiao Huang
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Salam Sammour
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Priyamvada Acharya
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Biochemistry, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA
- Robert H. Carnahan
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Ted M. Ross
- Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA; Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA
- Barton F. Haynes
- Departments of Medicine and Immunology, Duke University, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
- Maria Hadjifrangiskou
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- James E. Crowe, Jr.
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Justin R. Bailey
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Spyros Kalams
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Lynn Morris
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
- Ivelin S. Georgiev
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Computer Science, Vanderbilt University, Nashville, TN 37232, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA; Program in Computational Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 2
p. 112044
Abstract
Summary: Despite prolific efforts to characterize the antibody response to human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) mono-infections, the response to chronic co-infection with these two ever-evolving viruses is poorly understood. Here, we investigate the antibody repertoire of a chronically HIV-1/HCV co-infected individual using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq). We identify five HIV-1/HCV cross-reactive antibodies demonstrating binding and functional cross-reactivity between HIV-1 and HCV envelope glycoproteins. All five antibodies show exceptional HCV neutralization breadth and effector functions against both HIV-1 and HCV. One antibody, mAb688, also cross-reacts with influenza and coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examine the development of these antibodies using next-generation sequencing analysis and lineage tracing and find that somatic hypermutation established and enhanced this reactivity. These antibodies provide a potential future direction for therapeutic and vaccine development against current and emerging infectious diseases. More broadly, chronic co-infection represents a complex immunological challenge that can provide insights into the fundamental rules that underly antibody-antigen specificity.
