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● Isolation of human neutralizing antibodies against RSV from the convalescent children.
● One potent monoclonal antibody RV11 potently neutralizes both RSV A and B subtypes.
● RV11 binds to a conserved epitope across site Ⅳ/Ⅴ of the fusion glycoprotein in its prefusion state.
● RV11 is synergistic with a small molecular inhibitor ziresovir and a site Ø neutralizing mAb.
Respiratory syncytial virus (RSV) is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly. Passive immunoprophylaxis with monoclonal antibody (mAb) has been approved to prevent morbidity and mortality from RSV infection in infants. Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion (F) glycoprotein as bait. One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay, and protected mice from RSV infection in vivo. An RV11 escape mutant was identified, which contains an S443P mutation in F protein. Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites Ⅳ and Ⅴ of the F glycoprotein. RV11 showed a strong synergistic effect when combined with two RSV antivirals, an F-targeting small molecular inhibitor ziresovir and a site Ø neutralizing mAb D25 (the parental mAb for nirsevimab). The study extended our knowledge to the neutralizing and protective epitopes of RSV, and the mAb RV11 deserves further development for clinical translation.
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