Respiratory syncytial virus fusion protein (RSV F) (RSV F)

The Respiratory syncytial virus (RSV) fusion (F) protein is a type I transmembrane surface glycoprotein essential for viral entry into host cells. It facilitates the fusion of the viral envelope with the host cell membrane, a process triggered by a dramatic conformational change from a metastable prefusion state (pre-F) to a stable postfusion state (post-F) (McLellan et al., 2013, Science). The RSVPreF3 antigen is a recombinant version of this protein specifically engineered and stabilized in the prefusion conformation to preserve highly potent neutralizing epitopes, such as Site Ø, which are absent in the postfusion form (Crank et al., 2019, Science). By presenting these specific epitopes to the immune system, the antigen elicits a robust neutralizing antibody response. This target is the primary component of modern RSV vaccines, such as Arexvy, which are used to prevent lower respiratory tract disease in older adults (Papi et al., 2023, NEJM). Additionally, the F protein is the target for monoclonal antibodies like Palivizumab and Nirsevimab used for passive immunoprophylaxis in infants (Simoes et al., 2022, NEJM). Targeting the prefusion state is considered superior to the postfusion state because the most potent neutralizing antibodies in human sera are specific to the pre-F conformation.

Other names

RSVPreF3RSV F proteinFusion glycoproteinPre-F proteinPrefusion-stabilized RSV F proteinF0 protein

Neutralization of viral entry by binding to the prefusion conformation of the F protein, thereby preventing the structural transition required for membrane fusion between the virus and the host cell (McLellan et al., 2013, Science).