Human Anti-RSV F Recombinant Antibody (clone MEDI8897) (CAT#: PABS-0166)

Figure 1 RSV-neutralizing antibody levels after a single IM dose of MEDI8897 or placebo. Data points represent the mean RSV A2 neutralizing antibody levels on a log2 scale.

Error bars represent the standard deviations (SDs). LLOQ indicates lower limit of quantitation.

Domachowske, J. B., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Villafana, T., ... & Griffin, M. P. (2018). Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. The Pediatric infectious disease journal, 37(9), 886.

Figure 2 Binding of MEDI8897* to RSV F B9320 variants determined by SPR.

Sensorgrams are shown for the binding of MEDI8897* Fab to immobilized RSV F B9320 DS-Cav1 variants. The concentration of each Fab injection increased 2-fold from 1.25 nM to 40 nM. The red lines represent the best fit of the data to a 1:1 binding model.

Domachowske, J. B., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Villafana, T., ... & Griffin, M. P. (2018). Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. The Pediatric infectious disease journal, 37(9), 886.

Figure 3 RSV neutralization by mAbs

Neutralization activity curves of mAbs MEDI8897* (green), D25 (black), motavizumab (red), and palivizumab (purple) against RSV A2 and B9320 laboratory strains.

Domachowske, J. B., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Villafana, T., ... & Griffin, M. P. (2018). Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. The Pediatric infectious disease journal, 37(9), 886.

Figure 4 RSV neutralization by mAbs

RSV neutralization IC₅₀ values of MEDI8897* (green) and palivizumab (purple) against a large panel of RSV A and B isolates. The line represents geometric mean IC50.

Domachowske, J. B., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Villafana, T., ... & Griffin, M. P. (2018). Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. The Pediatric infectious disease journal, 37(9), 886.

Figure 5 Binding site of MEDI8897* on RSV F and sequence conservation.

(A) Schematic of mature RSV F polyprotein indicating salient features: F2 and F1 subunits (the N- and C-terminal polypeptides, respectively, after proteolysis of F protein precursor); C, cysteine, FP, fusion peptide; HR1, heptad repeat 1; HR2, heptad repeat 2; TM, transmembrane. The epitopes are indicated, and the amino acid residues with side chains thatform hydrogen bonds or salt bridges with MEDI8897* are colored blue. (B) Sequence conservation of F residues in the region recognized by MEDI8897* was analyzed against 2088 F protein sequences from GenBank and an internal database.

Domachowske, J. B., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Villafana, T., ... & Griffin, M. P. (2018). Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. The Pediatric infectious disease journal, 37(9), 886.

Figure 6 Prophylactic efficacy of MEDI8897* and determination of EC90 in RSV-infected cotton rats.

(A and B) Animals were administered with MEDI8897* or palivizumab by intramuscular injection at the indicated concentrations 1 day before challenge with RSV. The viral titers in the lungs and nose were determined by plaque assay on day 4 after infection with (A) RSV A2 or (B) RSV B9320. Error bars indicate mean values with SD (n = 6 to 8). The dotted line in (A) and (B) indicates the limit of detection. Serum concentrations of human IgG were measured by ELISA.

Domachowske, J. B., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Villafana, T., ... & Griffin, M. P. (2018). Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. The Pediatric infectious disease journal, 37(9), 886.

Figure 7 Prophylactic efficacy of MEDI8897* and determination of EC90 in RSV-infected cotton rats.

(C andD) The serum level of MEDI8897* that correlates with EC90 or>3-log reductions compared to control in RSV viral titers in the lungs of infected rats was calculated using a nonlinear regression analysis for (C) RSV A2 and (D) RSV B9320. The dotted line in (C) and (D) represents EC90 for viral reduction. Data are representative of two to three independent experiments (A and B) or were from the combined two to three experiments (C and D).

Domachowske, J. B., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Villafana, T., ... & Griffin, M. P. (2018). Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. The Pediatric infectious disease journal, 37(9), 886.