RSV
RSV-A genotypic drug resistance interpretation’s algorithm (November 2025 – Version n°3)
ANRS-MIE – Respiratory viruses group
GENOTYPE INTERPRETATION: MONOCLONAL ANTIBODIES TO RSV F PROTEIN
| Mutations associated with resistance | Mutations associated with «possible resistance» | Described polymorphisms in epitope Ø without impact on sensitivity (fold change <5) | |
| Nirsevimab | ▪ N67I + N208Y [4] *Note that N67I or N208Y alone are not associated with resistance | ▪ K68E [1] ▪ K209E [8] | ▪ N63T/S [3,7] ▪ I64V [1] ▪ K65R [1] ▪ E66K/G [3,7] ▪ K68N/R [1,4] ▪ N197K/H/D [1] ▪ I199M [1] ▪ L204I [1] ▪ I206T/I [1,3,4] ▪ V207I [1] ▪ K209R [7] ▪ Q210L [1] ▪ S211R [7] |
| Palivizumab | ▪ K272M/T [1] ▪ S275F [1] | Not listed | ▪ E66G |
| Clesrovimab | ▪ S443P [9,10,11] ▪ G446E/R/W [9,10,11,12] | Not listed | ▪ I432T [9,10] ▪ D440G [9] |
RSV-B genotypic drug resistance interpretation’s algorithm (November 2025 – Version n°3)
ANRS-MIE – Respiratory viruses group
GENOTYPE INTERPRETATION: MONOCLONAL ANTIBODIES TO RSV F PROTEIN
| Mutations associated with resistance | Mutations associated with « possible resistance » | Described polymorphisms in epitope Ø without impact on sensitivity (fold change <5) | |
| Nirsevimab |
|
|
|
| Palivizumab |  K272N/Q [1] | N63S [1] K272R [1] | Not listed |
| Clesrovimab | S443P[9,10] G446E/W/R [9,10] | Not listed | I432V/T [9,10] K445R [9,10] |
1 – Wilkins D, Langedijk AC, Lebbink RJ, Morehouse C, Abram ME, Ahani B, et al. Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data. The Lancet Infectious Diseases. 1 juill 2023;23(7):856‑66.
2 – Abram ME, Ahani B, Tabor DE, Fernandes F, Wilkins D, Aksyuk AA, et al. 94. Pooled analysis of nirsevimab resistance through 150 days post dose in preterm and term infants. Open Forum Infect Dis. 2022 Dec 15;9(Suppl 2):ofac492.019. doi:10.1093/ofid/ofac492.019
3 – Zhu Q, McLellan JS, Kallewaard NL, Ulbrandt ND, Palaszynski S, Zhang J, et al. A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci Transl Med . 2017 May 3;9(388):eaaj1928. doi: 10.1126/scitranslmed.aaj1928.
4 – Zhu Q, Lu B, McTamney P, Palaszynski S, Diallo S, Ren K, et al. Prevalence and Significance of Substitutions in the Fusion Protein of Respiratory Syncytial Virus Resulting in Neutralization Escape From Antibody MEDI8897. J Infect Dis. 2018 Jul 13;218(4):572-580. doi: 10.1093/infdis/jiy189.
5 – EMA. European Medicines Agency. 2022 [cited 6 sept 2023]. Beyfortus. Available on: https://www.ema.europa.eu/en/medicines/human/EPAR/beyfortus
6 – Ahani B, Tuffy KM, Aksyuk AA, Wilkins D, Abram ME, Dagan R, et al. Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials. Nat Commun. 2023 Jul 19;14(1):4347. doi: 10.1038/s41467-023-40057-8.
7 – Fourati S, Reslan A, Bourret J, Casalegno JS, Rahou Y, Chollet L, et al. Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study. Lancet Infect Dis. 2025 Mar;25(3):301-311. doi: 10.1016/S1473-3099(24)00570-X.
8 – Fourati S, Reslan A, Bourret J, Casalegno JS, Rahou Y, Softic L, et al. Real-World Emergence of Nirsevimab Resistance in RSV-B Breakthrough Infections. Rochester, NY: Social Science Research Network; 2025 [cited 2025 Nov 10]. Available from: https://papers.ssrn.com/abstract=5427106
9 – Tang A, Chen Z, He X, Wang D, Fridman A, Railkar RA, et al. Comprehensive analysis of clesrovimab epitope substitutions at site IV of the RSV F protein from the literature, GenBank, and clinical trials [Internet]. 13th International RSV Symposium (RSV2025); 2025 Mar 12; Iguazu, Brazil. Available from: https://bsac.org.uk/wp-content/uploads/2025/05/35.pdf
10 – U.S. Food and Drug Administration. ENFLONSIA (clesrovimab-cfor) injection – Highlights of Prescribing Information [Internet]. U.S. Food and Drug Administration. 2025 [cited 2025 Nov 10]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761432s000lbl.pdf
11 – Tang A, Chen Z, Cox KS, Su HP, Callahan C, Fridman A, et al. A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein. Nat Commun. 2019 Sep 12;10:4153.
12 – Wetzke M, Le DB, Tometten I, Ritter S, Lübke N, Timm J, et al. Prevalence of Resistance-Associated Mutations in RSV F Protein Against Monoclonal Antibodies Prior to Widespread Implementation: Findings From a Prospective German Pediatric Cohort. Influenza Other Respir Viruses. 2025 Sep 18;19(9):e70164.