Neutralizing epitopes on the respiratory syncytial virus fusion glycoprotein

•X-ray crystal structures of prefusion and postfusion RSV F have been determined.•Antibodies specific for the prefusion conformation are extremely potent.•Select antibodies neutralize both RSV and human metapneumovirus.•Structure-based vaccine design has produced promising immunogens. Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis, but despite decades of research a safe and effective vaccine has remained elusive. The viral fusion glycoprotein (RSV F) plays an obligatory role in the entry process and is the major target of neutralizing antibodies, making it an attractive target for vaccine development. This review will summarize the recently determined structures of RSV F in the prefusion and postfusion conformations and describe the location and properties of neutralizing epitopes on RSV F, including the newly identified prefusion-specific epitopes. The influence of these findings on vaccine development will also be discussed, with a focus on the rational design and optimization of vaccine antigens.