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

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Science Immunology  09 Mar 2018:
Vol. 3, Issue 21, eaar3534
DOI: 10.1126/sciimmunol.aar3534

Structural insights

Respiratory syncytial virus (RSV) causes respiratory infections associated with severe morbidity and mortality in infants, young children, and the elderly, and currently, no licensed vaccine exists. Fedechkin et al. now describe cocrystal structures of the RSV G glycoprotein conserved central domain (CCD) bound by two different broadly neutralizing monoclonal antibodies (mAbs). Both mAbs bind to conformational epitopes on this highly conserved region. The RSV G CCD can activate CX3CR1, and this activity can be blocked by binding of these mAbs. These findings provide structural insights into how neutralizing mAbs interact with the RSV G glycoprotein and may advance the development of new RSV vaccines and therapeutics.


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.

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