Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses
Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAbs) from a CHIKV-convalescent donor. We characterized 33 human mAbs that cross-reacted with CHIKV and MAYV and engaged multiple epitopes on the E1 and E2 glycoproteins. We identified five mAbs that target distinct regions of the B domain of E2 and potently neutralize multiple alphaviruses with differential breadth of inhibition. These broadly neutralizing mAbs (bNAbs) contain few somatic mutations and inferred germline-revertants retained neutralizing capacity. Two bNAbs, DC2.M16 and DC2.M357, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice. These findings enhance our understanding of the cross-reactive and cross-protective antibody response to human alphavirus infections.
| Errataetall: |
CommentIn: Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):. - PMID 34625494 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 118(2021), 37 vom: 14. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Malonis, Ryan J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.12.2021 Date Revised 11.03.2022 published: Print CommentIn: Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):. - PMID 34625494 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2100104118 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330502050 |
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| 100 | 1 | |a Malonis, Ryan J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses |
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| 500 | |a CommentIn: Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):. - PMID 34625494 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAbs) from a CHIKV-convalescent donor. We characterized 33 human mAbs that cross-reacted with CHIKV and MAYV and engaged multiple epitopes on the E1 and E2 glycoproteins. We identified five mAbs that target distinct regions of the B domain of E2 and potently neutralize multiple alphaviruses with differential breadth of inhibition. These broadly neutralizing mAbs (bNAbs) contain few somatic mutations and inferred germline-revertants retained neutralizing capacity. Two bNAbs, DC2.M16 and DC2.M357, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice. These findings enhance our understanding of the cross-reactive and cross-protective antibody response to human alphavirus infections | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Mayaro virus | |
| 650 | 4 | |a alphaviruses | |
| 650 | 4 | |a broadly neutralizing antibodies | |
| 650 | 4 | |a heterologous immunity | |
| 650 | 4 | |a monoclonal antibodies | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Broadly Neutralizing Antibodies |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 700 | 1 | |a Earnest, James T |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Arthur S |e verfasserin |4 aut | |
| 700 | 1 | |a Angeliadis, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Holtsberg, Frederick W |e verfasserin |4 aut | |
| 700 | 1 | |a Aman, M Javad |e verfasserin |4 aut | |
| 700 | 1 | |a Jangra, Rohit K |e verfasserin |4 aut | |
| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
| 700 | 1 | |a Daily, Johanna P |e verfasserin |4 aut | |
| 700 | 1 | |a Diamond, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Kielian, Margaret |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Jonathan R |e verfasserin |4 aut | |
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