Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design
Abstract Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known corr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-92886-w |
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| author | Maria G. Juarez Sara M. O’Rourke John V. Dzimianski Delia Gagnon Gabriel Penunuri Vitor H. B. Serrão Russell B. Corbett-Detig Lawrence M. Kauvar Rebecca M. DuBois |
| author_facet | Maria G. Juarez Sara M. O’Rourke John V. Dzimianski Delia Gagnon Gabriel Penunuri Vitor H. B. Serrão Russell B. Corbett-Detig Lawrence M. Kauvar Rebecca M. DuBois |
| author_sort | Maria G. Juarez |
| collection | DOAJ |
| description | Abstract Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known correlate of protection. Previously, several broadly reactive, high-affinity anti-RSV G human monoclonal antibodies were isolated from RSV-exposed individuals and were shown to be protective in vitro and in vivo. Here, we determined the structures of three of these antibodies in complex with RSV G and defined distinct conformational epitopes comprised of highly conserved RSV G residues. Binding competition and structural studies demonstrated that this highly conserved region displays two non-overlapping antigenic sites. Analyses of anti-RSV G antibody sequences reveal that antigenic site flexibility may promote the elicitation of diverse antibody germlines. Together, these findings provide a foundation for next-generation RSV prophylactics, and they expand concepts in vaccine design for the elicitation of germline lineage-diverse, broadly reactive, high-affinity antibodies. |
| format | Article |
| id | doaj-art-d2ceaad0afc14ee9983289f2b4084d68 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d2ceaad0afc14ee9983289f2b4084d682025-08-20T02:56:06ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-92886-wStructures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine designMaria G. Juarez0Sara M. O’Rourke1John V. Dzimianski2Delia Gagnon3Gabriel Penunuri4Vitor H. B. Serrão5Russell B. Corbett-Detig6Lawrence M. Kauvar7Rebecca M. DuBois8Department of Molecular, Cell, and Developmental Biology, University of California Santa CruzDepartment of Biomolecular Engineering, University of California Santa CruzDepartment of Biomolecular Engineering, University of California Santa CruzDepartment of Biomolecular Engineering, University of California Santa CruzDepartment of Biomolecular Engineering, University of California Santa CruzDepartment of Chemistry & Biochemistry, University of California Santa CruzDepartment of Biomolecular Engineering, University of California Santa CruzTrellis Bioscience, IncDepartment of Biomolecular Engineering, University of California Santa CruzAbstract Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known correlate of protection. Previously, several broadly reactive, high-affinity anti-RSV G human monoclonal antibodies were isolated from RSV-exposed individuals and were shown to be protective in vitro and in vivo. Here, we determined the structures of three of these antibodies in complex with RSV G and defined distinct conformational epitopes comprised of highly conserved RSV G residues. Binding competition and structural studies demonstrated that this highly conserved region displays two non-overlapping antigenic sites. Analyses of anti-RSV G antibody sequences reveal that antigenic site flexibility may promote the elicitation of diverse antibody germlines. Together, these findings provide a foundation for next-generation RSV prophylactics, and they expand concepts in vaccine design for the elicitation of germline lineage-diverse, broadly reactive, high-affinity antibodies.https://doi.org/10.1038/s41598-025-92886-w |
| spellingShingle | Maria G. Juarez Sara M. O’Rourke John V. Dzimianski Delia Gagnon Gabriel Penunuri Vitor H. B. Serrão Russell B. Corbett-Detig Lawrence M. Kauvar Rebecca M. DuBois Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design Scientific Reports |
| title | Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design |
| title_full | Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design |
| title_fullStr | Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design |
| title_full_unstemmed | Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design |
| title_short | Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design |
| title_sort | structures of respiratory syncytial virus g bound to broadly reactive antibodies provide insights into vaccine design |
| url | https://doi.org/10.1038/s41598-025-92886-w |
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