New and Emerging Passive Immunization Strategies for the Prevention of RSV Infection During Infancy

To date, safe and effective strategies to prevent medically attended respiratory syncytial virus (RSV) illness across the infant population have been limited to passive immunoprophylaxis for those at highest risk. While active vaccination strategies are finally available to protect adults 60 years and older from serious RSV infection, safe and effective vaccines for use in children have yet to emerge. In contrast, passive immunization strategies designed to protect all infants against RSV has finally met with success, with 2 new strategies approved by the US Food and Drug Administration during the second half of 2023. The first RSV passive immunization strategy to gain licensure for use in all infants is an extended half-life monoclonal antibody directed against an antigenic binding site on the RSV-F prefusion protein, a conformation not known to exist until 2013. The second novel passive immunization strategy approved during 2023 that has the potential to protect much of the infant population from RSV during young infancy centers on boosting preexisting RSV immunity during pregnancy using a prefusion RSV-F vaccine. The resulting boosted humoral immune response to RSV in the mother becomes part of the transplacental antibody endowment that is actively transported across the placenta to provide protection to those babies born at or near term. This review describes how and why these advances came to fruition seemingly "all at once" and provides insight into other passive immunization approaches that remain under development.