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.
Competing Interest Statement
JDB consults for Apriori Bio, Invivyd, the Vaccine Company, GSK, and Pfizer. JDB is an inventor on Fred Hutch licensed patents related to deep mutational scanning of viral proteins. ALG reports contract testing to UW from Abbott, Cepheid, Novavax, Pfizer, Janssen and Hologic, research support from Gilead, outside of the described work. MB has received research support from Merck, GSK, and AstraZeneka, and consults for Merck, AstraZeneka, and Ivivyd. The King lab has received unrelated sponsored research agreements from Pfizer and GSK.
