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

Summary

Using cryo-EM structures of three broadly reactive human monoclonal antibodies bound to RSV G, the authors define conserved, conformational epitopes that comprise two non-overlapping antigenic sites. Sequence and competition analyses suggest antigenic site flexibility fosters diverse germline usage, informing designs to elicit broadly reactive anti-G responses.

Key Findings

• Cryo-EM structures of three human broadly reactive anti-RSV G antibodies revealed conserved, conformational epitopes comprising two non-overlapping antigenic sites.
• Binding competition and structural data identified a highly conserved region on G with dual antigenic topology.
• Antibody sequence analyses indicate antigenic site flexibility that may promote elicitation of diverse antibody germlines, supporting broadly reactive vaccine design.

Clinical Implications

Guides the rational design of RSV vaccines or monoclonals that target G, potentially improving breadth and durability of protection and complementing F-based products now in use.

Limitations

• Preclinical mechanistic study without direct clinical efficacy testing
• Scope limited to three monoclonal antibodies and selected G regions

Future Directions

Design and immunogenicity testing of G-based or G+F combination immunogens; evaluation of breadth, durability, and protection in animal models and early human trials.