Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design.

Maria G Juarez; Sara M O'Rourke; John V Dzimianski; Delia Gagnon; Gabriel Penunuri; Vitor H B Serr&#xe3;o; Russell B Corbett-Detig; Lawrence M Kauvar; Rebecca M DuBois

doi:10.1038/s41598-025-92886-w

PubMed · 40082629

Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design.

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

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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.

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Humans Antibodies, Viral Respiratory Syncytial Virus, Human Respiratory Syncytial Virus Infections Respiratory Syncytial Virus Vaccines Viral Fusion Proteins Epitopes Antibodies, Monoclonal Protein Binding Journal Article

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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. 2025-03-13. Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design.. https://doi.org/10.1038/s41598-025-92886-w

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