Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection.
Enterovirus A71 (EV-A71) infection is a major cause of severe hand, foot and mouth disease (HFMD) in young children. The characteristics of EV-A71 neutralizing antibodies in HFMD patients are not well understood. In this study, we identified and cloned EV-A71-neutralizing antibodies by single cell R...
| Main Authors: | , , , , , , , |
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| פורמט: | Article |
| שפה: | English |
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Public Library of Science (PLoS)
2023-06-01
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| סדרה: | PLoS Pathogens |
| גישה מקוונת: | https://doi.org/10.1371/journal.ppat.1011420 |
| _version_ | 1827917593060573184 |
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| author | Lei You Junbo Chen Yibing Cheng Yu Li Yao-Qing Chen Tianlei Ying Lance Turtle Hongjie Yu |
| author_facet | Lei You Junbo Chen Yibing Cheng Yu Li Yao-Qing Chen Tianlei Ying Lance Turtle Hongjie Yu |
| author_sort | Lei You |
| collection | DOAJ |
| description | Enterovirus A71 (EV-A71) infection is a major cause of severe hand, foot and mouth disease (HFMD) in young children. The characteristics of EV-A71 neutralizing antibodies in HFMD patients are not well understood. In this study, we identified and cloned EV-A71-neutralizing antibodies by single cell RNA and B cell receptor sequencing of peripheral blood mononuclear cells. From 145 plasmablasts, we identified two IgG1 monoclonal antibodies (mAbs) and six IgM mAbs that neutralized EV-A71. Four of the IgM mAbs harbor germline variable sequences and neutralize EV-A71 potently. Two genetically similar IgM antibodies from two patients have recurrent heavy chain variable domain gene usage and similar complementarity-determining region 3 sequences. We mapped the residues of EV-A71 critical for neutralization through selection of virus variants resistant to antibody neutralization in the presence of neutralizing mAbs. The residues critical for neutralization are conserved among EV-A71 genotypes. Epitopes for the two genetically similar antibodies overlap with the SCARB2 binding site of EV-A71. We used escape variants to measure the epitope-specific antibody response in acute phase serum samples from EV-A71 infected HFMD patients. We found that these epitopes are immunogenic and contributed to the neutralizing antibody response against the virus. Our findings advance understanding of antibody response to EV-A71 infection in young children and have translational potential: the IgM mAbs could potentially be used for prevention or treatment of EV-A71 infections. |
| first_indexed | 2024-03-13T03:30:36Z |
| format | Article |
| id | doaj.art-a09a839b9bee48d2a2a8f4618f83fcf9 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-13T03:30:36Z |
| publishDate | 2023-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a09a839b9bee48d2a2a8f4618f83fcf92023-06-24T05:31:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-06-01196e101142010.1371/journal.ppat.1011420Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection.Lei YouJunbo ChenYibing ChengYu LiYao-Qing ChenTianlei YingLance TurtleHongjie YuEnterovirus A71 (EV-A71) infection is a major cause of severe hand, foot and mouth disease (HFMD) in young children. The characteristics of EV-A71 neutralizing antibodies in HFMD patients are not well understood. In this study, we identified and cloned EV-A71-neutralizing antibodies by single cell RNA and B cell receptor sequencing of peripheral blood mononuclear cells. From 145 plasmablasts, we identified two IgG1 monoclonal antibodies (mAbs) and six IgM mAbs that neutralized EV-A71. Four of the IgM mAbs harbor germline variable sequences and neutralize EV-A71 potently. Two genetically similar IgM antibodies from two patients have recurrent heavy chain variable domain gene usage and similar complementarity-determining region 3 sequences. We mapped the residues of EV-A71 critical for neutralization through selection of virus variants resistant to antibody neutralization in the presence of neutralizing mAbs. The residues critical for neutralization are conserved among EV-A71 genotypes. Epitopes for the two genetically similar antibodies overlap with the SCARB2 binding site of EV-A71. We used escape variants to measure the epitope-specific antibody response in acute phase serum samples from EV-A71 infected HFMD patients. We found that these epitopes are immunogenic and contributed to the neutralizing antibody response against the virus. Our findings advance understanding of antibody response to EV-A71 infection in young children and have translational potential: the IgM mAbs could potentially be used for prevention or treatment of EV-A71 infections.https://doi.org/10.1371/journal.ppat.1011420 |
| spellingShingle | Lei You Junbo Chen Yibing Cheng Yu Li Yao-Qing Chen Tianlei Ying Lance Turtle Hongjie Yu Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection. PLoS Pathogens |
| title | Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection. |
| title_full | Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection. |
| title_fullStr | Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection. |
| title_full_unstemmed | Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection. |
| title_short | Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection. |
| title_sort | antibody signatures in hospitalized hand foot and mouth disease patients with acute enterovirus a71 infection |
| url | https://doi.org/10.1371/journal.ppat.1011420 |
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