Human B-cell receptors specific for prefusion RSV F (preF-BCRs)

Human B-cell receptors (BCRs) specific for the prefusion conformation of the Respiratory Syncytial Virus (RSV) fusion (F) protein are the primary sensors on B cells that initiate a protective immune response against RSV (McLellan et al., 2013). These receptors recognize unique, highly neutralizing epitopes—such as site Ø and site V—that are present only on the metastable prefusion form of the F protein and are lost upon its transition to the postfusion state (Graham, 2019). Engagement of these BCRs by prefusion-stabilized F antigens (used in modern vaccines) or natural infection triggers B-cell expansion, affinity maturation, and differentiation into memory B cells and plasma cells (Scharffenberger et al., 2024). The resulting antibodies are significantly more potent at neutralizing the virus than those targeting the postfusion form, making these BCRs the central target for germline-targeting and structure-based vaccine design. Successful activation of this specific BCR repertoire is the basis for the efficacy of recently approved RSV vaccines like Arexvy and Abrysvo, which aim to elicit high titers of prefusion-specific neutralizing antibodies to prevent severe lower respiratory tract disease (NIH, 2023). These BCRs also serve as the template for therapeutic monoclonal antibodies, such as nirsevimab, which provide passive immunity to high-risk populations.

Other names

RSV F-specific B-cell receptorsPrefusion RSV F-specific BCRspreF-specific memory B-cell receptorsSite Ø-specific B-cell receptorsRSV-neutralizing B-cell receptors

Vaccines act as immunogens that bind to and cross-link these BCRs, triggering B-cell proliferation, affinity maturation, and differentiation into antibody-secreting plasma cells.