Table 3.
Mortality associated with I.V. administration of engineered anthrax lethal toxins: Determining I.V. MTD6
| Description of Agent | Dose (μg) | # Mice | % Survival at Day 14 | Log-Ranka (P) | ||
|---|---|---|---|---|---|---|
| Control Groups | vehicle control | PBS | --- | 10 | 100 | --- |
|
| ||||||
| wild-type anthrax lethal toxin | PrAg-WT + LF | 6/2 | 5 | 0 | <0.01 | |
|
| ||||||
| MMP-activated PrAg + enzymatically-inactive LF | PrAg-L1 + LF-E687A | 50/16.7 | 6 | 50 | 0.01 | |
|
| ||||||
| MMP-activated PrAg alone | PrAg-L1 | 50 | 5 | 60 | 0.03 | |
|
| ||||||
| uPA-activated PrAg alone | PrAg-U2 | 50 | 4 | 75 | n.s. | |
|
| ||||||
| dual MMP/uPA-activated PrAg alone | IC-PrAg (PrAg-L1-I210A + PrAg-U2-R200A) | 25/25 | 5 | 80 | n.s. | |
|
| ||||||
| Experimental Groups [I.V. MTD6 Determination] | MMP-activated anthrax lethal toxin | PrAg-L1 + LF | 15/5 | 4 | 0 | <0.01 |
| 12/4 | 9 | 66 | 0.02 | |||
| 9/3 | 10 | 70 | n.s. | |||
| 6/2b | 10 | 100 | n.s. | |||
| 3/1 | 6 | 100 | n.s. | |||
|
| ||||||
| uPA-activated anthrax lethal toxin | PrAg-U2 + LF | 15/5 | 8 | 75 | n.s. | |
| 12/4b | 13 | 100 | n.s. | |||
| 9/3 | 11 | 100 | n.s. | |||
|
| ||||||
| Dual MMP/uPA-activated anthrax lethal toxin | IC-PrAg (PrAg-L1-I210A + PrAg-U2-R200A) + LF | 7.5/7.5/5 | 5 | 80 | n.s. | |
| 6/6/4b | 12 | 100 | n.s. | |||
| 4.5/4.5/3 | 11 | 100 | n.s. | |||
a
Log-Rank tests compare the Kaplan-Meier survival curve of the vehicle control (PBS) cohort with that of the indicated cohort
b
I.V. MTD6
Abbreviations: n.s., not significant