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The Respiratory syncytial virus (RSV) prefusion F glycoprotein antigen is a metastable class I viral fusion protein located on the viral surface, essential for mediating the fusion of the viral envelope with the host cell membrane (McLellan et al., 2013, Science). It is the primary target for neutralizing antibodies because it contains highly potent epitopes, such as Site Ø and Site V, which are lost when the protein transitions to its stable postfusion conformation (Graham, 2017, Annual Review of Medicine). Therapeutic strategies targeting this antigen include monoclonal antibodies like Nirsevimab, which binds to Site Ø to block viral entry, and recombinant vaccines like Arexvy and Abrysvo that stabilize the protein in its prefusion state to elicit a robust immune response (FDA, 2023). This target is critical for preventing severe lower respiratory tract disease (LRTD), bronchiolitis, and pneumonia in vulnerable populations, including infants and older adults (CDC, 2024). By maintaining the prefusion structure, these interventions achieve significantly higher neutralizing antibody titers compared to older vaccine candidates that used the postfusion form.
Neutralization of viral entry by binding to prefusion-specific epitopes and preventing the conformational change required for membrane fusion.
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