Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein

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Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children, yet an efficacious vaccine remains unavailable. Antibodies that preferentially recognize the prefusion conformation of the fusion (F) glycoprotein, particularly those that bind antigenic site Ø at the membrane-distal apex, potently neutralize infection and have aided vaccine design. Here we characterize AM14, a potent human antibody, which we show recognizes a novel epitope midway between the membrane-proximal region and the apex of the prefusion F trimer. The epitope is evenly distributed across two protomers, causing AM14 to be uniquely trimer-specific and, surprisingly, cleavage-dependent. These results indicate that the prefusion trimer is antigenically distinct from the monomer. Our findings also demonstrate that epitopes other than site Ø can be the target of extremely potent neutralizing antibodies and thus provide a new target for structure-based vaccine design. Recognition of this novel epitope could make AM14 an ideal candidate for strategies that combine passive prophylaxis with vaccination, since binding of AM14 would not block elicitation of antibodies against site Ø. Due to its unique specificity, AM14 will also be valuable for probing the conformation of RSV F-based vaccine antigens designed to be in the furin-cleaved trimeric prefusion conformation.

Vyšlo v časopise: Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005035
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005035

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