bioRxivMarch 12, 2025

RSV F evolution escapes some monoclonal antibodies but does not strongly erode neutralization by human polyclonal sera

Cassandra AL Simonich, Teagan A McMahon, Xiaohui Ju, Timothy C Yu, Natalie Brunette, Terry Stevens-Ayers, Michael J Boeckh, Neil P King, Alexander L Greninger, Jesse D Bloom
doi:10.1101/2025.03.11.642476

Abstract

Vaccines and monoclonal antibodies targeting the respiratory syncytial virus (RSV) fusion protein (F) have recently begun to be widely used to protect infants and high-risk adults. Some other viral proteins evolve to erode polyclonal antibody neutralization and escape individual monoclonal antibodies. However, little is known about how RSV F evolution affects antibodies. Here we develop an experimental system for measuring neutralization titers against RSV F using pseudotyped lentiviral particles. This system is easily adaptable to evaluate neutralization of relevant clinical strains. We apply this system to demonstrate that natural evolution of RSV F leads to escape from some monoclonal antibodies, but at most modestly affects neutralization by polyclonal serum antibodies. Overall, our work sheds light on RSV antigenic evolution and describes a tool to measure the ability of antibodies and sera to neutralize contemporary RSV strains.