Genomic Surveillance and Antigenic Characterization of Respiratory Syncytial Virus (RSV) in Spain During the 2023-2024 Season of Nirsevimab Administration.

Respiratory Syncytial Virus (RSV) is a leading cause of respiratory infections in infants and older adults. In Spain, surveillance is supported by the SiVIRA system and the RELECOV genomic sequencing network. The 2023-2024 season marked the first nationwide administration of nirsevimab, a monoclonal antibody for preventing severe RSV in infants. This study analyzes the genomic evolution of RSV during this period, focusing on potential escape mutations in the F protein. RSV-A showed high genetic diversity with eleven circulating lineages, while RSV-B was dominated by lineage B.D.E.1. Phylogenetic analysis revealed three distinct B.D.4.1.1 groups, one sharing mutations with B.D.E.1 in the nirsevimab binding site. Despite these changes, neutralization assays confirmed that nirsevimab and other monoclonal antibodies remained effective. No significant antigenic drift compromising immunoprophylaxis was observed. These findings support the continued efficacy of nirsevimab and highlight the importance of genomic surveillance for tracking RSV evolution and informing future immunization strategies.