B cell repertoire sequencing of HIV-1 pediatric elite-neutralizers identifies multiple broadly neutralizing antibody clonotypes
Copyright © 2024 Kumar, Bajpai, Joyce, Kabra, Lodha, Burton, Briney and Luthra..
Introduction: A limited subset of HIV-1 infected adult individuals typically after at least 2-3 years of chronic infection, develop broadly neutralizing antibodies (bnAbs), suggesting that highly conserved neutralizing epitopes on the HIV-1 envelope glycoprotein are difficult for B cell receptors to effectively target, during natural infection. Recent studies have shown the evolution of bnAbs in HIV-1 infected infants.
Methods: We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1.
Results: BCR-seq of both twins revealed convergent antibody characteristics including V-gene use, CDRH3 lengths and somatic hypermutation (SHM). Further, antibody clonotypes with genetic features similar to highly potent bnAbs isolated from adults showed ongoing development in donor AIIMS_330 but not in AIIMS_329, corroborating our earlier findings based on plasma bnAbs responses. An increase in SHM was observed in sequences of the IgA isotype from AIIMS_330.
Discussion: This study suggests that children living with chronic HIV-1 can develop clonotypes of HIV-1 bnAbs against multiple envelope epitopes similar to those isolated from adults, highlighting that such B cells could be steered to elicit bnAbs responses through vaccines aimed to induce bnAbs against HIV-1 in a broad range of people including children.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 22., Seite 1272493 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kumar, Sanjeev [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.03.2024 Date Revised 25.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2024.1272493 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM36923720X |
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| 100 | 1 | |a Kumar, Sanjeev |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a B cell repertoire sequencing of HIV-1 pediatric elite-neutralizers identifies multiple broadly neutralizing antibody clonotypes |
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| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Kumar, Bajpai, Joyce, Kabra, Lodha, Burton, Briney and Luthra. | ||
| 520 | |a Introduction: A limited subset of HIV-1 infected adult individuals typically after at least 2-3 years of chronic infection, develop broadly neutralizing antibodies (bnAbs), suggesting that highly conserved neutralizing epitopes on the HIV-1 envelope glycoprotein are difficult for B cell receptors to effectively target, during natural infection. Recent studies have shown the evolution of bnAbs in HIV-1 infected infants | ||
| 520 | |a Methods: We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1 | ||
| 520 | |a Results: BCR-seq of both twins revealed convergent antibody characteristics including V-gene use, CDRH3 lengths and somatic hypermutation (SHM). Further, antibody clonotypes with genetic features similar to highly potent bnAbs isolated from adults showed ongoing development in donor AIIMS_330 but not in AIIMS_329, corroborating our earlier findings based on plasma bnAbs responses. An increase in SHM was observed in sequences of the IgA isotype from AIIMS_330 | ||
| 520 | |a Discussion: This study suggests that children living with chronic HIV-1 can develop clonotypes of HIV-1 bnAbs against multiple envelope epitopes similar to those isolated from adults, highlighting that such B cells could be steered to elicit bnAbs responses through vaccines aimed to induce bnAbs against HIV-1 in a broad range of people including children | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B cell repertoire sequencing | |
| 650 | 4 | |a HIV-1 | |
| 650 | 4 | |a bnAbs | |
| 650 | 4 | |a children | |
| 650 | 4 | |a clonotypes | |
| 650 | 4 | |a elite-neutralizers | |
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| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
| 650 | 7 | |a Antibodies |2 NLM | |
| 650 | 7 | |a Antigens, Viral |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 700 | 1 | |a Bajpai, Prashant |e verfasserin |4 aut | |
| 700 | 1 | |a Joyce, Collin |e verfasserin |4 aut | |
| 700 | 1 | |a Kabra, Sushil Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Lodha, Rakesh |e verfasserin |4 aut | |
| 700 | 1 | |a Burton, Dennis R |e verfasserin |4 aut | |
| 700 | 1 | |a Briney, Bryan |e verfasserin |4 aut | |
| 700 | 1 | |a Luthra, Kalpana |e verfasserin |4 aut | |
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