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Sci Immunol. 2018 Mar 9;3(21). pii: eaar3534. doi: 10.1126/sciimmunol.aar3534. Epub 2018 Mar 9.

Structures of respiratory syncytial virus G antigen bound to broadly neutralizing antibodies.

Author information

1
Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
2
Trellis Bioscience LLC, Menlo Park, CA 94025, USA.
3
Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. rmdubois@ucsc.edu.

Abstract

Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in young children and the elderly. The viral envelope G glycoprotein contributes to pathogenesis through its roles in host cell attachment and modulation of host immunity. Although the G glycoprotein is a target of protective RSV-neutralizing antibodies, its development as a vaccine antigen has been hindered by its heterogeneous glycosylation and sequence variability outside a conserved central domain (CCD). We describe the cocrystal structures of two high-affinity broadly neutralizing human monoclonal antibodies bound to the RSV G CCD. The antibodies bind to neighboring conformational epitopes, which we named antigenic sites γ1 and γ2, that span a highly conserved surface, illuminating an important region of vulnerability. We further show that isolated RSV G CCD activates the chemokine receptor CX3CR1 and that antibodies block this activity. These studies provide a template for rational vaccine design targeting this key contributor to RSV disease.

PMID:
29523582
DOI:
10.1126/sciimmunol.aar3534

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