Nirsevimab (Beyfortus), an antibody targeting respiratory syncytial virus (RSV), is indicated in neonates and infants to prevent bronchiolitis. Available since September 2023, its widespread use could lead to resistance mutations. However, according to the French POLYRES study on the prospective monitoring of nirsevimab, published recently in Lancet infectious diseasesthese mutations are very rare at this stage.

“The low prevalence of nirsevimab resistance mutations in treated patients is reassuring. However, escape mutations have been observed in a few RSV-B in treated patients, urging caution and highlighting the importance of active molecular surveillance in the context of future broader global use of nirsevimab. commented Slim Fourati, MD, PhD, head of the Virology Unit of the Henri Mondor Hospital, Université Paris-Est and INSERM U955, Paris, France, and lead author, in a press release.

Theoretical risk of emerging variants

The 2023-2024 season marked the first preventive RSV vaccination campaign with nirsevimab, which showed a positive impact on prevent bronchiolitis in infants.

Nirsevimab targets a specific epitope of the F fusion protein located on the surface of RSV and involved in viral replication, thereby blocking the virus. As RSV is a variable virus, there is a theoretical risk of variants with nirsevimab resistance mutations emerging, even without antibody-mediated selection pressure.

Observational and multicenter study

During phase 2b/3 clinical trials, only 48 cases of RSV in infected children treated with nirsevimab were analyzed, with escape mutations identified in two cases. Nirsevimab is now available for all infantsand the risk of resistance mutations could increase with widespread preventive use of the drug.

This concern led to the POLYRES study, which aimed to assess the risk of virological resistance to nirsevimab in a larger sample via a large-scale, real-world, multicenter observational study conducted during the 2023-2024 winter season.

“This study is the largest virological failure surveillance study of nirsevimab to date. It was made possible thanks to a collaborative synergy with the ANRS MIE (Emerging Infectious Diseases) consortium of virologists. This is a national project that will identify the phenomenon of resistance associated with the widespread use of this drug. This type of study is essential to analyze the evolutionary dynamics of viruses, in light of existing medical solutions,” explained the corresponding author of the study Marie-Anne Rameix-Welti, MD, PhD, head of the National Reference Center for Respiratory Viruses at the Pasteur Institute and the Molecular Mechanisms of Pneumovirus Multiplication (M3P) Unit, Université Paris-Saclay-Versailles Saint-Quentin, INSERM U1173, Paris, France.

The study included 695 RSV-infected infants, 349 of whom received nirsevimab prophylaxis. RSV-A was predominant this season, found in 86.6% of infected children. The study teams analyzed the characteristics of RSV-A and RSV-B strains present in nasopharyngeal samples collected as part of routine care.

The complete viral genome sequence was determined, specifically to identify mutations in the nirsevimab binding site (genotypic analysis). They also studied the ability of nirsevimab to inhibit viral replication in cell cultures (phenotypic analysis).

Analysis of 472 RSV-A samples (half from treated children) revealed no nirsevimab resistance mutations in the F protein epitope site.

Among the 73 children infected with RSV-B, 24 had received prophylaxis with nirsevimab. In these 24 children, two RSV-B isolates showed nirsevimab resistance mutations – one previously known and the other identified for the first time. According to the authors“Results from the POLYRES study support the continued use of nirsevimab for RSV prophylaxis in all newborns worldwide. »

This study was funded by the ANRS Emerging Infectious Diseases and the French Ministry of Health.

This story was translated from The French edition of Medscape using multiple editorial tools, including AI, in the process. Human editors reviewed this content before publication.