RSV
RSV-A genotypic drug resistance interpretation’s algorithm (October 2023 – Version n°1)
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] | N63T/S [3] I64V [1] K65R [1] E66K [3] K68N/R [1,4] N197K/H/D [1] I199M [1] L204I [1] I206T/I [1,3,4] V207I [1] Q210L [1] |
| Palivizumab | ▪ K272M/T [1] ▪ S275F [1] | Not listed | Not listed |
RSV-B genotypic drug resistance interpretation’s algorithm (October 2023 – Version n°1)
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 | ▪ I64T [6] ▪ I64T + K68E [2,6] ▪ K68E/Q [1,6] ▪ K68N + N201S [4,5] ▪ K68N + N208S [4,5] ▪ N201S/T [1,4] ▪ N208S/D [2,4-6] | ▪ K65Q + S211N [3] ▪ K68N [1,4] ▪ K65Q/T [3] | N63S [1] K65R [1] E66D [1,3,4] T67A/I [1,3] K68R [1] N197D/S [1,3] I206M [1,6] Q209R/K/L [1,3,6] Q210H [4] S211N/I [1,6] |
| Palivizumab | ▪ K272N/Q [1] ▪ K272N/Q [1] | ▪ N63S [1] ▪ K272R [1] | Not listed |
Monoclonal antibodies to RSV F protein
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 Infectious Diseases. 1 déc 2022;9(Supplement_2):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. Science Translational Medicine. 3 mai 2017;9(388):eaaj1928.
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. The Journal of Infectious Diseases. 13 juill 2018;218(4):572‑80.
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. 19 juill 2023;14(1):4347.