Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor.

  • Pilewski KA, Wall S, Richardson SI, Manamela NP, Clark K, Hermanus T, Binshtein E, Venkat R, Sautto GA, Kramer KJ, Shiakolas AR, Setliff I, Salas J, Mapengo RE, Suryadevara N, Brannon JR, Beebout CJ, Parks R, Raju N, Frumento N, Walker LM, Fechter EF, Qin JS, Murji AA, Janowska K, Thakur B, Lindenberger J, May AJ, Huang X, Sammour S, Acharya P, Carnahan RH, Ross TM, Haynes BF, Hadjifrangiskou M, Crowe JE, Bailey JR, Kalams S, Morris L, Georgiev IS. Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor. Cell reports. 2023 Jan 27;42(42). 112044 p. PMID: 36708513 [PubMed] PMCID: PMC10372200 NIHMSID: NIHMS1878913.


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.