학술논문
Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor
Document Type
article
Author
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
Source
Cell Reports, Vol 42, Iss 2, Pp 112044- (2023)
Subject
Language
English
ISSN
2211-1247
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.