TY - JOUR
T1 - Genetic variability of respiratory syncytial virus and its impact on monoclonal antibody binding sites
T2 - a national cross-sectional study during the 2023-2024 season
AU - Piralla, Antonio
AU - Romano, Greta
AU - Acciarri, Carla
AU - Menzo, Stefano
AU - Renteria, Sara Uceda
AU - Callegaro, Annapaola
AU - Galli, Cristina
AU - Pellegrinelli, Laura
AU - Pierangeli, Alessandra
AU - Fracella, Matteo
AU - Novazzi, Federica
AU - Mancini, Nicasio
AU - Russo, Cristina
AU - Ranno, Stefania
AU - Vian, Elisa
AU - Damian, Donna
AU - Pagani, Elisabetta
AU - Masi, Elisa
AU - Pomari, Elena
AU - Castilletti, Concetta
AU - Allice, Tiziano Giacomo
AU - Cerutti, Francesco
AU - Mancon, Alessandro
AU - Micheli, Valeria
AU - Lalle, Eleonora
AU - Maggi, Fabrizio
AU - Sallustio, Anna
AU - Chironna, Maria
AU - Tiberio, Claudia
AU - Esposito, Martina
AU - Ferrari, Guglielmo
AU - Antonelli, Guido
AU - Baldanti, Fausto
AU - Pariani, Elena
AU - GLIViRe Study Group
N1 - Lehr-KH Provincial Hospital of Bolzano (SABES-ASDAA), Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität, Bolzano, Italy
PY - 2025/12/3
Y1 - 2025/12/3
N2 - Background: Respiratory syncytial virus is a primary cause of acute lower respiratory tract infections globally. As preventive tools such as vaccines and monoclonal antibodies begin to enter clinical use, baseline genomic data are critical to evaluate their future impact and detect potential resistance-related mutations. The working group on respiratory viral infections (GLIViRe) conducted this multicenter study to characterize the genetic profile of RSV circulating in Italy during the 2023-2024 season, immediately prior to the introduction of immunoprophylactic interventions. The study focused on identifying mutations in the F protein at mAb binding sites for palivizumab, nirsevimab, RSM01, TNM-001, and clesrovimab. Methods: A total of 350 respiratory samples positive for RSV collected from patients with influenza-like illness (ILI) or acute respiratory infection (ARI), during the 2023-2024 season from 15 Italian laboratories were selected for sequence analysis. The F gene sequencing was performed on 287 RSV-A and 63 RSV-B samples using Sanger or next-generation sequencing. Phylogenetic analysis was conducted using IQ-TREE, with the integration of global data via NextStrain. Key mutations were mapped onto the F protein structure using ChimeraX and Protein Data Bank models. Shannon entropy was used to assess amino acid variability. Results: RSV-A samples predominantly belonged to the emerging A.D, A.D.1, and A.D.3 clades, while RSV-B samples mainly clustered in the B & sdot;D lineage. Key substitutions were detected at antigenic site & empty;, particularly at the nirsevimab and RSM01 interfaces. No changes occurred at the palivizumab/TNM-001 site II. All mutations of interest were exposed to the F protein surface. Conclusions: This study provides a critical genomic snapshot of RSV in Italy prior to the introduction of vaccines and mAbs. Continuous surveillance is essential for monitoring viral evolution and supporting the long-term effectiveness of future immunization strategies.
AB - Background: Respiratory syncytial virus is a primary cause of acute lower respiratory tract infections globally. As preventive tools such as vaccines and monoclonal antibodies begin to enter clinical use, baseline genomic data are critical to evaluate their future impact and detect potential resistance-related mutations. The working group on respiratory viral infections (GLIViRe) conducted this multicenter study to characterize the genetic profile of RSV circulating in Italy during the 2023-2024 season, immediately prior to the introduction of immunoprophylactic interventions. The study focused on identifying mutations in the F protein at mAb binding sites for palivizumab, nirsevimab, RSM01, TNM-001, and clesrovimab. Methods: A total of 350 respiratory samples positive for RSV collected from patients with influenza-like illness (ILI) or acute respiratory infection (ARI), during the 2023-2024 season from 15 Italian laboratories were selected for sequence analysis. The F gene sequencing was performed on 287 RSV-A and 63 RSV-B samples using Sanger or next-generation sequencing. Phylogenetic analysis was conducted using IQ-TREE, with the integration of global data via NextStrain. Key mutations were mapped onto the F protein structure using ChimeraX and Protein Data Bank models. Shannon entropy was used to assess amino acid variability. Results: RSV-A samples predominantly belonged to the emerging A.D, A.D.1, and A.D.3 clades, while RSV-B samples mainly clustered in the B & sdot;D lineage. Key substitutions were detected at antigenic site & empty;, particularly at the nirsevimab and RSM01 interfaces. No changes occurred at the palivizumab/TNM-001 site II. All mutations of interest were exposed to the F protein surface. Conclusions: This study provides a critical genomic snapshot of RSV in Italy prior to the introduction of vaccines and mAbs. Continuous surveillance is essential for monitoring viral evolution and supporting the long-term effectiveness of future immunization strategies.
KW - Humans
KW - Respiratory Syncytial Virus Infections/virology
KW - Respiratory Syncytial Virus, Human/genetics
KW - Italy/epidemiology
KW - Antibodies, Monoclonal/metabolism
KW - Cross-Sectional Studies
KW - Genetic Variation
KW - Viral Fusion Proteins/genetics
KW - Phylogeny
KW - Female
KW - Male
KW - Binding Sites, Antibody
KW - Mutation
KW - Infant
KW - Antiviral Agents/therapeutic use
KW - Seasons
KW - Child, Preschool
KW - Palivizumab
KW - Drug Resistance, Viral/genetics
KW - Child
KW - Binding Sites
U2 - 10.1016/j.intimp.2025.115591
DO - 10.1016/j.intimp.2025.115591
M3 - Original Article
C2 - 40997502
SN - 1567-5769
VL - 166
SP - 115591
JO - INTERNATIONAL IMMUNOPHARMACOLOGY
JF - INTERNATIONAL IMMUNOPHARMACOLOGY
M1 - 115591
ER -