Bivalent RSV prefusion F vaccination elicits effective neutralization of contemporary and monoclonal antibody-resistant RSV strains

Abstract Respiratory syncytial virus (RSV) is the leading global cause of serious respiratory disease in infants and an important respiratory pathogen in older adults. The RSV prefusion F protein (preF) is a major target of neutralizing antibodies shown to protect against RSV disease. The bivalent preF protein subunit vaccine (RSVpreF; Abrysvo®) contains stabilized preF antigens representing the two major RSV subgroups, RSV A and RSV B. Here, we characterized the neutralizing activity of adult RSVpreF immune sera against a panel of 65 contemporary, globally circulating RSV A and RSV B clinical isolates, containing various amino acid substitutions across the five major antigenic sites of RSV F (Ø, I, II, III, V). Monoclonal Ab-resistant mutant strains (MARMs) displaying in vitro resistance to nirsevimab, clesrovimab, and palivizumab (up to 300,000-fold resistance over the parental strain) were also evaluated. RSVpreF immune sera effectively neutralized both the panel of global clinical isolates and all MARMs tested. These findings demonstrate that the bivalent RSVpreF polyclonal response maintains robust neutralizing activity against circulating RSV A and B strains, including those that escape RSV F mAbs, and provides broad protective immunity against RSV.