Biomedical Engineering Reference
In-Depth Information
Figure
4.9.
Cotton rat PK study: BAL levels of motavizumab variants. Motavizumab is undetec-
table at 21 days. (See the insert for color representation of this figure.)
there was no statistical difference in the levels of motavizumab in serum, BAL, and lung
homogenate for the variants tested.
Similar results were obtained previously with palivizumab variants. Palivizumab
was administered to cotton rats and levels were measured in serum, BAL, and lung
homogenates. The results showed no statistical difference in the levels of palivizumab in
serum (Fig. 4.11), BAL, and lung homogenate (data not shown).
Published data have previously shown that antibody-mediated inhibition of RSV
infection in a cotton rat model is not dependent on the Fc portion of the IgG1 molecule
[24]. Similarly, we found that palivizumab Fab and F(ab
0
)
2
variants protect against RSV
infection in an in vivo cotton rat model (Fig. 4.12). Since the Fab and F(ab
0
)
2
variants lack
the Fc portion of the molecule and, therefore, are completely devoid of oligosaccharides,
these data provide supportive evidence that oligosaccharides are not required for the
mechanism of action of antibody-dependent neutralization of RSV activity.
Untreated motavizumab, G0-enriched, and G2-enriched samples were also eval-
uated as a prophylaxis for RSVinfection in cotton rats. Rats were dosed with untreated,
Figure
4.10.
Cotton rat PK study: lung homogenate levels of motavizumab variants. Mota-
vizumab is undetectable at 21 days. (See the insert for color representation of this figure.)
