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Publication Abstract from PubMed

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 gamma1 and gamma2, 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.

Structures of respiratory syncytial virus G antigen bound to broadly neutralizing antibodies.,Fedechkin SO, George NL, Wolff JT, Kauvar LM, DuBois RM Sci Immunol. 2018 Mar 9;3(21). pii: 3/21/eaar3534. doi:, 10.1126/sciimmunol.aar3534. Epub 2018 Mar 9. PMID:29523582^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.