Table 4.
Group # | Description* | IFN-γ | Fecal IgA | IL-17A | Bone Marrow ASC IgA | Bone Marrow ASC IgG | serum IgGT | serum IgG2a/IgG1 ratio | Immuno-genicity Score (female) | Immuno-genicity Score (male) | Overall Immuno-genicity Score | Overall Adjuvant Stability Score** | Combined Overall Score |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
7 | PO + antioxidant | 0.984 | 0.981 | 0.861 | 0.919 | 0.914 | 0.822 | 0.990 | 0.896 | 0.920 | 0.932 | 0.886 | 0.909 |
5 | PO + tonicity agent | 0.971 | 0.990 | 0.868 | 0.839 | 0.752 | 0.746 | 0.590 | 0.854 | 0.833 | 0.859 | 0.683 | 0.766 |
15 | DPPC, Mid ratio | 0.932 | 0.874 | 0.871 | 0.924 | 0.937 | 0.912 | 0.493 | 0.903 | 0.778 | 0.857 | 0.669 | 0.757 |
3 | PO | 0.912 | 0.936 | 0.621 | 0.845 | 0.868 | 0.740 | 0.736 | 0.834 | 0.757 | 0.815 | 0.687 | 0.749 |
19 | DSPC, Mid ratio | 0.963 | 0.715 | 0.873 | 0.861 | 0.919 | 0.823 | 0.745 | 0.941 | 0.703 | 0.840 | 0.598 | 0.709 |
12 | DMPC, Mid ratio | 0.978 | 0.762 | 0.844 | 0.694 | 0.691 | 0.990 | 0.433 | 0.765 | 0.771 | 0.781 | 0.628 | 0.700 |
17 | DOPC, High ratio | 0.975 | 0.908 | 0.886 | 0.721 | 0.795 | 0.904 | 0.393 | 0.720 | 0.874 | 0.818 | 0.591 | 0.696 |
11 | DMPC, Low ratio | 0.952 | 0.858 | 0.681 | 0.782 | 0.867 | 0.858 | 0.614 | 0.844 | 0.749 | 0.810 | 0.562 | 0.675 |
16 | DSPC, High ratio | 0.987 | 0.842 | 0.990 | 0.832 | 0.850 | 0.878 | 0.497 | 0.817 | 0.877 | 0.859 | 0.526 | 0.672 |
8 | DPPC, Low ratio | 0.990 | 0.863 | 0.818 | 0.653 | 0.689 | 0.829 | 0.863 | 0.687 | 0.898 | 0.830 | 0.450 | 0.611 |
9 | DOPC, Mid ratio | 0.973 | 0.658 | 0.695 | 0.649 | 0.786 | 0.737 | 0.633 | 0.788 | 0.666 | 0.738 | 0.504 | 0.610 |
14 | DSPC, Low ratio | 0.971 | 0.971 | 0.935 | 0.990 | 0.990 | 0.936 | 0.376 | 0.931 | 0.826 | 0.889 | 0.369 | 0.573 |
10 | DOPC, Low ratio | 0.974 | 0.796 | 0.755 | 0.831 | 0.855 | 0.801 | 0.523 | 0.792 | 0.775 | 0.804 | 0.241 | 0.440 |
2 | POC | 0.890 | 0.960 | 0.558 | 0.815 | 0.801 | 0.651 | 0.575 | 0.780 | 0.725 | 0.766 | 0.231 | 0.420 |
13 | DPPC, High ratio | 0.966 | 0.962 | 0.921 | 0.981 | 0.963 | 0.946 | 0.128 | 0.891 | 0.697 | 0.803 | 0.195 | 0.396 |
18 | DMPC, High ratio | 0.967 | 0.719 | 0.694 | 0.870 | 0.866 | 0.814 | 0.559 | 0.735 | 0.804 | 0.785 | 0.137 | 0.328 |
20 | PSO (less LecA) | 0.862 | 0.010 | 0.281 | 0.135 | 0.247 | 0.104 | 0.027 | 0.077 | 0.161 | 0.116 | 0.669 | 0.279 |
4 | PSO (less 3M052) | 0.809 | 0.655 | 0.314 | 0.495 | 0.462 | 0.452 | 0.010 | 0.570 | 0.305 | 0.379 | 0.108 | 0.203 |
6 | PO + viscosity agent | 0.947 | 0.814 | 0.699 | 0.663 | 0.648 | 0.777 | 0.674 | 0.722 | 0.781 | 0.766 | N/A | N/A |
1 | LecA alone | 0.010 | 0.041 | 0.010 | 0.010 | 0.010 | 0.010 | 0.195 | 0.013 | 0.023 | 0.017 | N/A | N/A |
LecA dose was 10 µg for all groups except for the POC formulation (5 µg) and the PSO-less LecA (0.5 µg). *PO, Predicted Optimal formulation from dose optimization DOE; PSO, Predicted Sub-Optimal formulations from dose optimization DOE; POC, Proof-of-Concept formulation (same as group #15 from the dose optimization DOE); DMPC, DPPC, DSPC, DOPC refers to acyl chain structure of liposomal lipids; High, Mid, Low refers to phospholipid: PEGylated lipid ratios. See Supplementary Table 7 for additional formulation composition details. **See Supplementary Table 8 for detailed adjuvant stability results. Color scale: higher desirability index values are light blue, lower desirability index values are dark blue.