Respiratory syncytial virus fusion glycoprotein F (prefusion-stabilized FA2 variant) (RSV pre-F FA2)

The Respiratory syncytial virus (RSV) fusion glycoprotein F is a Class I viral fusion protein that mediates the critical step of membrane fusion between the virus and the host cell (UniProt P03420). It exists in two distinct conformations: a metastable prefusion (pre-F) state and a stable postfusion (post-F) state. The FA2 variant is a specifically engineered version of the RSV subgroup A (strain A2) F protein, stabilized in the prefusion conformation through mutations such as those described in structure-based design studies (McLellan et al., Science 2013). This stabilization is essential because the pre-F form contains the most potent neutralizing epitopes, including Site Ø and Site V, which are lost when the protein triggers into the post-F state (Swanson et al., Science Translational Medicine 2020). The FA2 variant serves as a primary antigen in bivalent vaccines like Abrysvo, designed to elicit high titers of neutralizing antibodies to prevent lower respiratory tract disease (LRTD) such as bronchiolitis and pneumonia in infants and older adults (FDA, Abrysvo Prescribing Information). Monoclonal antibodies like Nirsevimab also target these prefusion-specific sites to provide passive immunity against RSV infection (Hammitt et al., N Engl J Med 2022). By maintaining the protein in its most vulnerable state, the FA2 variant allows the immune system to recognize and block the virus before it can enter host cells. This approach has revolutionized RSV prevention, addressing a long-standing challenge in vaccine development.

Other names

RSV F proteinPrefusion FRSVpreFRSV A2 prefusion FStabilized RSV fusion proteinRSVpreF ARSV subgroup A prefusion F

Neutralization of viral infectivity by binding to the prefusion conformation of the F protein, thereby preventing the structural transition to the postfusion state required for membrane fusion and viral entry into host cells.