119 - Longitudinal amino acid mutations in the fusion-protein of RSV and their effects on the sensitivity to specific antibodies and replicative capacity

Publication Number: 119.5582

Hisao Okabe, Fukushima Medical University: Fukushima Kenritsu Ika Daigaku, Fukushima-City, Fukushima, Japan; Koichi Hashimoto, Fukushima Medical University, Fukushima, Fukushima, Japan; Sakurako Norito, Fukushima Medical University, Fukushima, Fukushima, Japan; Takashi Ono, Fukushima medical university, Fukushima, Fukushima, Japan; Yohei Kume, Fukushima medical university, Fukushima, Fukushima, Japan; Yuichiro Asano, matsudo city general hospital, matsudo, Chiba, Japan; Mina Chishiki, Fukushima Medical University, Fukushima, Fukushima, Japan; Hajime Maeda, School of Medicine, Fukushima Medical University, Fukushima, Fukushima, Japan; Fumi Mashiyama, Hoshi General Hospital, Koriyama, Fukushima, Japan; Masatoki Sato, Fukushima Medical University, Fukushima, Fukushima, Japan; Mitsuaki Hosoya, Fukushima Medical University, Fukushima, Fukushima, Japan; Hayato Go, Fukushima Medical Iniversity, Fukushima, Fukushima, Japan

Background: Information on amino acid (AA) mutations and monoclonal antibody (mAb) sensitivity of the F protein of respiratory syncytial virus (RSV) remains insufficient.

Objective: We analyzed AA mutations in major neutralizing epitopes of the F protein and the mAb sensitivity and replicative capacity of the mutant strains.

Design/Methods: We analyzed F protein genes of 236 RSV strains isolated from children hospitalized with an RSV infection in Fukushima Prefecture, Japan between 2008 and 2023. AA mutations were detected at sites II, V, and Ø. We conducted neutralization assays using site-specific mAbs to investigate the relationship between AA mutations and mAb sensitivity. Finally, we examined the replication capacities of these viruses.

Results: Site II: RSV strains isolated from children receiving palivizumab treatment exhibited the K272M mutation in RSV-A and K272E mutation in RSV-B, showing reduced sensitivity to the site II-specific antibody. Site V: In RSV-A, >50% strains isolated since 2022 harbored the V178I mutation; however, this did not result in reduced sensitivity to site V-specific antibodies. In RSV-B, L172Q/S173L mutant strains became predominant around 2016, leading to reduced sensitivity to site V-specific antibodies. Site Ø: No AA mutations were detected in RSV-A. In RSV-B, the I206M/Q209R mutant strain became predominant around 2018 and several other AA mutations were detected. However, none resulted in reduced sensitivity to site Ø-specific antibodies. The replication capacities of predominant AA mutant strains did not decrease.

Conclusion(s): The RSV F protein in Japan has evolved naturally with corresponding changes in antibody sensitivity. Therefore, AA mutations and antibody sensitivity must be monitored.