Convergent evolution and targeting of diverse E2 epitopes by human broadly neutralizing antibodies are associated with HCV clearance
Copyright © 2024. Published by Elsevier Inc..
The early appearance of broadly neutralizing antibodies (bNAbs) in serum is associated with spontaneous hepatitis C virus (HCV) clearance, but to date, the majority of bNAbs have been isolated from chronically infected donors. Most of these bNAbs use the VH1-69 gene segment and target the envelope glycoprotein E2 front layer. Here, we performed longitudinal B cell receptor (BCR) repertoire analysis on an elite neutralizer who spontaneously cleared multiple HCV infections. We isolated 10,680 E2-reactive B cells, performed BCR sequencing, characterized monoclonal B cell cultures, and isolated bNAbs. In contrast to what has been seen in chronically infected donors, the bNAbs used a variety of VH genes and targeted at least three distinct E2 antigenic sites, including sites previously thought to be non-neutralizing. Diverse front-layer-reactive bNAb lineages evolved convergently, acquiring breadth-enhancing somatic mutations. These findings demonstrate that HCV clearance-associated bNAbs are genetically diverse and bind distinct antigenic sites that should be the target of vaccine-induced bNAbs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57 |
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| Enthalten in: |
Immunity - 57(2024), 4 vom: 09. Apr., Seite 890-903.e6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ogega, Clinton O [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.04.2024 Date Revised 12.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.immuni.2024.03.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The early appearance of broadly neutralizing antibodies (bNAbs) in serum is associated with spontaneous hepatitis C virus (HCV) clearance, but to date, the majority of bNAbs have been isolated from chronically infected donors. Most of these bNAbs use the VH1-69 gene segment and target the envelope glycoprotein E2 front layer. Here, we performed longitudinal B cell receptor (BCR) repertoire analysis on an elite neutralizer who spontaneously cleared multiple HCV infections. We isolated 10,680 E2-reactive B cells, performed BCR sequencing, characterized monoclonal B cell cultures, and isolated bNAbs. In contrast to what has been seen in chronically infected donors, the bNAbs used a variety of VH genes and targeted at least three distinct E2 antigenic sites, including sites previously thought to be non-neutralizing. Diverse front-layer-reactive bNAb lineages evolved convergently, acquiring breadth-enhancing somatic mutations. These findings demonstrate that HCV clearance-associated bNAbs are genetically diverse and bind distinct antigenic sites that should be the target of vaccine-induced bNAbs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a B cells | |
| 650 | 4 | |a BCR sequencing | |
| 650 | 4 | |a HCV | |
| 650 | 4 | |a antibody evolution | |
| 650 | 4 | |a broadly neutralizing antibodies | |
| 650 | 4 | |a hepatitis C virus | |
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| 700 | 1 | |a Skinner, Nicole E |e verfasserin |4 aut | |
| 700 | 1 | |a Schoenle, Marta V |e verfasserin |4 aut | |
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| 700 | 1 | |a Frumento, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Wright, Desiree A |e verfasserin |4 aut | |
| 700 | 1 | |a Paul, Harry T |e verfasserin |4 aut | |
| 700 | 1 | |a Sinnis-Bourozikas, Ariadne |e verfasserin |4 aut | |
| 700 | 1 | |a Clark, Kaitlyn E |e verfasserin |4 aut | |
| 700 | 1 | |a Figueroa, Alexis |e verfasserin |4 aut | |
| 700 | 1 | |a Bjorkman, Pamela J |e verfasserin |4 aut | |
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| 700 | 1 | |a Flyak, Andrew I |e verfasserin |4 aut | |
| 700 | 1 | |a Bailey, Justin R |e verfasserin |4 aut | |
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