Nirsevimab Resistance Mutations Rare in RSV, Study Shows

Nirsevimab (Beyfortus), an antibody targeting respiratory syncytial virus (RSV), is indicated for newborns and infants to prevent bronchiolitis. Available since September 2023, its widespread use may lead to resistance mutations. However, according to the French POLYRES study on prospective monitoring of nirsevimab, published recently in The Lancet Infectious Diseases, these 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-Bs from treated patients, prompting caution and highlighting the importance of active molecular surveillance in the context of future wider global use of nirsevimab,” commented Slim Fourati, MD, PhD, head of the Virology Unit at Henri Mondor Hospital, Paris-Est University 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 immunization campaign against RSV with nirsevimab, which has shown a positive impact on preventing bronchiolitis in infants.

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

Observational, Multicenter Study

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

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

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

The study included 695 infants with RSV infection, of whom 349 had 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 nirsevimab’s ability 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 nirsevimab prophylaxis. In these 24 children, two RSV-B isolates showed resistance mutations to nirsevimab — one previously known and the other identified for the first time. According to the authors, “the results of the POLYRES study support the continued use of nirsevimab for RSV prophylaxis in all newborns worldwide.”

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

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.