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TitleStructures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design.
Journal, issue, pagesSci Rep, Vol. 15, Issue 1, Page 8666, Year 2025
Publish dateMar 13, 2025
AuthorsMaria 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 /
PubMed AbstractRespiratory 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 ...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.
External linksSci Rep / PubMed:40082629 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.74 - 7.29 Å
Structure data

EMDB-47153: Single particle cryoelectron microscopy of respiratory syncytial virus G ectodomain in complex with Fabs 2D10 and 3D3
Method: EM (single particle) / Resolution: 7.29 Å

PDB-9cqa:
Structure of antibody 1G1 bound to the central conserved region of RSV G
Method: X-RAY DIFFRACTION / Resolution: 1.74 Å

PDB-9cqb:
Antibody 1G8 bound to the central conserved domain of RSV G
Method: X-RAY DIFFRACTION / Resolution: 2.5 Å

PDB-9cqd:
Antibody 2B11 bound to the central conserved domain of RSV G
Method: X-RAY DIFFRACTION / Resolution: 3.1 Å

Chemicals

ChemComp-SO4:
SULFATE ION

ChemComp-HOH:
WATER

Source
  • Respiratory syncytial virus
  • homo sapiens (human)
  • respiratory syncytial virus a2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / antibody / respiratory syncytial virus / G glycoprotein / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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