BackgroundHuman respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes.MethodsWe conducted a cohort study of children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between initial and subsequent RSV infections.ResultsWe examined 1802 children from May 2014 to January 2016 and collected 3471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein.ConclusionsAmino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.