Nirsevimab-resistant respiratory syncytial virus B (RSV-B) variants have been recognized in infants with breakthrough infections throughout routine medical use, in accordance with a nationwide observational examine from France. The findings present the primary large-scale real-world proof that resistance to the long-acting monoclonal antibody can emerge following prophylaxis, though researchers emphasise that resistant viruses stay confined to breakthrough instances.
Nirsevimab, which targets a conserved area of the RSV prefusion F protein, has remodeled prevention of extreme RSV illness in infants since its introduction. Scientific trials and early implementation research demonstrated excessive efficacy towards RSV-associated hospitalisation, however issues have continued over whether or not widespread use may drive viral evolution.
Researchers analysed greater than 1,000 toddler RSV instances
The multicentre POLYRES-2 examine examined RSV infections in 1,023 infants aged one yr or youthful who examined constructive for RSV throughout the 2024–2025 season in France, when RSV-B predominated nationally.
Researchers efficiently generated full-length viral genome sequences for 858 instances, together with 419 breakthrough infections in infants who had obtained nirsevimab and 439 infections in infants who had not obtained the antibody. Viral sequencing was mixed with laboratory neutralisation testing to find out whether or not recognized mutations lowered susceptibility to nirsevimab.
Resistance was primarily detected in RSV-B
Resistance-associated substitutions had been unusual in RSV-A, occurring in simply 1.0% of breakthrough infections. In distinction, resistant variants had been recognized in 12.5% of RSV-B breakthrough infections.
Greater than half of resistant RSV-B viruses carried mutations affecting amino acid residue 208 of the viral F protein, whereas researchers additionally recognized a number of beforehand unreported mutations able to decreasing susceptibility to nirsevimab.
Importantly, no resistant RSV strains had been detected in infants who had not obtained nirsevimab, suggesting these mutations emerged underneath selective stress following prophylaxis reasonably than circulating broadly locally.
Some resistant variants continued lengthy after prophylaxis
One notable discovering was the detection of an RSV-B variant carrying the F:N208S substitution virtually one yr after administration of nirsevimab.
The authors counsel this demonstrates that resistant viruses can persist longer than beforehand anticipated, highlighting the significance of monitoring viral evolution past the speedy RSV season.
Regardless of the emergence of resistance, the examine doesn’t counsel widespread remedy failure. As a substitute, resistance remained confined to a comparatively small proportion of breakthrough infections, and the general medical effectiveness of nirsevimab stays excessive.
Genomic surveillance can be crucial
The researchers conclude that integrating genomic sequencing with routine medical surveillance can be important as RSV immunisation programmes proceed to increase.
Monitoring resistant variants in real-world settings may assist determine rising escape mutations early, inform future monoclonal antibody improvement, and guarantee preventive methods stay efficient towards evolving RSV strains.
Whereas the findings warrant continued vigilance, the authors emphasise that the general advantages of nirsevimab prophylaxis stay substantial, with resistance presently representing solely a minority of breakthrough RSV-B infections.
Reference
Fourati S et al. Actual-world emergence of nirsevimab resistance in breakthrough infections with respiratory syncytial virus-B: a multicentre observational examine in France. The Lancet Microbe. 2026;DOI: 10.1016/j.lanmic.2026.101353.
