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Pilewski, Kelsey A.; Wall, Steven; Richardson, Simone I.; Manamela, Nelia P.; Clark, Kaitlyn; Hermanus, Tandile; Binshtein, Elad; Venkat, Rohit; Sautto, Giuseppe A.; Kramer, Kevin J.; Shiakolas, Andrea R.; Setliff, Ian; Salas, Jordan; Mapengo, Rutendo E.; Suryadevara, Naveen; Brannon, John R.; Beebout, Connor J.; Parks, Rob; Raju, Nagarajan; Frumento, Nicole; Walker, Lauren M.; Fechter, Emilee Friedman; Qin, Juliana S.; Murji, Amyn A.; Janowska, Katarzyna; Thakur, Bhishem; Lindenberger, Jared; May, Aaron J.; Huang, Xiao; Sammour, Salam; Acharya, Priyamvada; Carnahan, Robert H.; Ross, Ted M.; Haynes, Barton F.; Hadjifrangiskou, Maria; Crowe, James E.; Bailey, Justin R.; Kalams, Spyros; Morris, Lynn; Georgiev, Ivelin S.
Cell reports, 02/2023, Letnik: 42, Številka: 2Journal Article
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. Display omitted •LIBRA-seq is applied to characterize antibody responses to HIV-1/HCV co-infection•A diverse set of functional HIV-1/HCV cross-reactive antibodies are identified•A glycan-directed antibody exhibits exceptionally broad anti-viral recognition•Antibody somatic hypermutation is a major determinant for HIV-1/HCV cross-reactivity Pilewski et al. uses LIBRA-seq to identify multiple, functional HIV-1/HCV cross-reactive antibodies with diverse epitope specificities. This study identifies a glycan-reactive, broadly anti-viral antibody recognizing the NTD of SARS-CoV-2, in addition to antigens from multiple other viruses. The authors further show that somatic hypermutation both establishes and enhances HIV-1/HCV cross-reactivity.
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