Table 2 Genotype and phenotype of major variant substitutions in the F protein of the nirsevimab binding site and changes to nirsevimab susceptibility in participants with confirmed MA RSV LRTI meeting the primary case definition in MELODY through 150 days post-dose

From: Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials

Amino acid substitutions

Prevalence in surveillance studies (%)

Placebo

Nirsevimab

Total

Fold reduction in susceptibility

IC50 (ng/mL)

Nirsevimab

Palivizumab

Nirsevimab

Palivizumab

RSV A

 

(n = 23)

(n = 13)

(n = 36)

    

 No change

NA

23 (100%)

13 (100%)

36 (100%)

1.0

1.0

NA

NA

RSV B

 

(n = 29)

(n = 10)

(n = 39)

    

 No change

NA

1 (3.4%)

0

1 (2.6%)

1.0

1.0

NA

NA

 I206M:Q209R

66.0

6 (20.7%)

1 (10%)

7 (17.9%)

0.2

1.3

0.4

79.8

 I206Ma

68.9

28 (96.6%)

10 (100%)

38 (97.4%)

5

2.0

7.0

164.4

 Q209Rb

68.2

28 (96.6%)

10 (100%)

38 (97.4%)

0.5

3.1

0.9

213.7

 I206M:Q209R:S211N

1.1

22 (75.9%)

8 (80%)

30 (76.9%)

0.5

3.7

0.9

204.4

 S211Nc

1.1

22 (75.9%)

9 (90%)

31 (79.5%)

1.2

1.9

2.5

148.7

 L204S:I206M:Q209R:S211N

 

0

1 (10%)

1 (2.6%)

ND

ND

ND

ND

 L204Sd

 

0

1 (10%)

1 (2.6%)

ND

ND

ND

ND

  1. % of participants with RSV containing substitutions in the nirsevimab binding site is calculated based on the total number of participants meeting the primary endpoint of MA RSV LRTI in each treatment arm (placebo, nirsevimab) and each RSV strain (RSV A, RSV B).
  2. LRTI lower respiratory tract infection, MA medically attended, NA not available, ND not determined, NGS next-generation sequencing, RSV respiratory syncytial virus.
  3. aObserved as co-occurring with Q209R ± L204S, S211N.
  4. bObserved as co-occurring with I206M ± L204S, S211N.
  5. cObserved only as co-occurring with I206M:Q209R.
  6. dObserved only as co-occurring with I206M:Q209R:S211N.
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