A neutralizing antibody potently prevents RSV A and B infections by targeting a conserved region of the prefusion F

Abstract Respiratory syncytial virus (RSV) poses a significant public health challenge, especially among children. Although palivizumab and nirsevimab, neutralizing antibodies (nAbs) targeting the RSV F protein, have been used for prophylaxis, their limitations underscore the need for more effective alternatives. Here, we present a nAb 5B11 with exceptional potency against both RSV-A and RSV-B, outperforming the first FDA-approved nAb, palivizumab, and the long-acting nirsevimab. Cryo-electron microscopy study reveals 5B11’s mechanism of action by targeting a highly conserved epitope within site V, offering a promising strategy with lower risk of escape mutants. In vivo studies further confirm that low-dose 5B11 provides superior prophylactic efficacy, marking it as a potent candidate for broad RSV prevention.