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RSV-A genotypic drug resistance interpretation’s algorithm (November 2024 – Version n°2)

ANRS-MIE – Respiratory viruses group
GENOTYPE INTERPRETATION: MONOCLONAL ANTIBODIES TO RSV F PROTEIN

 Mutations associated with resistanceMutations 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 [3,7]
▪ 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 listedNot listed

RSV-B genotypic drug resistance interpretation’s algorithm (November 2024 – Version n°2)

ANRS-MIE – Respiratory viruses group
GENOTYPE INTERPRETATION: MONOCLONAL ANTIBODIES TO RSV F PROTEIN

 Mutations associated with resistanceMutations associated with « possible resistance »Described polymorphisms in epitope Ø without impact on sensitivity
(fold change <5)
Nirsevimab

▪ I64T [6]
▪ I64T + K68E [2,6]
▪ I64M + K65E [7]
▪ K68E/Q [1,6]
▪ K68N + N201S [4,5]
▪ K68N + N208S [4,5]
▪ N201S/T [1,4]
▪ N208S/D [2,4-7]

▪ K65Q + S211N [3]
▪ K68N [1,4]
▪ K65Q/T [3]

▪ N63S/D [1,7]
▪ I64V [7]
▪ K65R [1]
▪ E66D [1,3,4]
▪ T67A/I [1,3]
▪ K68R [1]
▪ N197D/S [1,3]
▪ I206M [1,6,7]
▪ Q209R/K/L [1,3,6,7]
▪ Q210H [4]
▪ S211N/I [1,6,7]

Palivizumab▪ K272N/Q [1]▪ N63S [1]
▪ K272R [1]		Not listed

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. Lancet Infect Dis. 2023 Jul;23(7):856-866. doi:
10.1016/S1473-3099(23)00062-2

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.