Table 1.
Summary of experimental data on nonviral Aβ DNA vaccine therapy against Alzheimer model mice
| Exp. | Group | Strain | No. of animals | Start of Tx, mo | Sampling, mo | Duration of Tx, mo | Regimen | Protocol | % Aβ burden (cortex) | % Aβ burden (hippocampus) | Inflammation | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Weekly | Biweekly | Monthly | Fc | IgL | K-Aβ | Emp | No Tx | Fc | IgL | K-Aβ | Emp | No Tx | CD5 | Mac3 | ||||||||
| 1 | 1 | Tg | 15 | 4 | 7 | 3 | Prophylactic | ×6 | ×3 | 15.5 | 18.2 | 31.4 | 93.1 | 100 | N.T. | N.T. | N.T. | N.T. | N.T. | Neg | Neg | |
| 2 | Tg | 32 | 4 | 9 | 5 | Prophylactic | ×6 | ×8 | 12.7 | 13.3 | 28.1 | 103 | 100 | N.T. | N.T. | N.T. | N.T. | N.T. | Neg | Neg | ||
| 3 | Tg | 17 | 4 | 12 | 8 | Prophylactic | ×6 | ×12 | 33.7 | 28.6 | 51.3 | 103 | 100 | 22 | 26 | 65.3 | 114 | 100 | Neg | Neg | ||
| 2 | 1 | Tg | 20 | 3 | 15 | 12 | Prophylactic | ×6 | ×24 | 30.6 | 37.2 | N.T. | 91.2 | 100 | 32.5 | 38.4 | N.T. | 96 | 100 | Neg | Neg | |
| 2 | Tg | 16 | 3 | 18 | 15 | Prophylactic | ×6 | ×29 | 38.5 | 46.2 | N.T. | 91.3 | 100 | 36.4 | 44.8 | N.T. | 99.5 | 100 | Neg | Neg | ||
| 3 | 1 | Tg | 23 | 12 | 15 | 3 | Therapeutic | ×6 | ×4 | 42.4 | 41.6 | N.T. | 98.1 | 100 | 40.3 | 43.5 | N.T. | 100 | 100 | Neg | Neg | |
| 2 | Tg | 19 | 12 | 18 | 6 | Therapeutic | ×6 | ×10 | 47 | 49.9 | N.T. | 96.7 | 100 | 38 | 46 | N.T. | 86.6 | 100 | Neg | Neg | ||
| 4 | 1 | Tg | 18 | 7 | 15 | 8 | Therapeutic | ×9 | 67.6 | 81.7 | N.T. | 90.6 | 100 | 69.4 | 73.9 | N.T. | 95.6 | 100 | Neg | Neg | ||
| 2 | Tg | 16 | 7 | 18 | 11 | Therapeutic | ×12 | 79.6 | 88.1 | N.T. | 91.7 | 100 | 74.8 | 75.6 | N.T. | 92 | 100 | Neg | Neg | |||
| 5 | 1 | B6 | 25 | 4 | 7 | 3 | – | ×6 | ×4 | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | Neg | Neg | |
| 2 | B6 | 25 | 4 | 9 | 5 | – | ×6 | ×9 | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | Neg | Neg | ||
| 3 | B6 | 24 | 4 | 12 | 8 | – | ×6 | ×14 | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | N.T. | Neg | Neg | ||
The vaccines were administered for the indicated duration to a large number of mice (176 APP23 and 74 B6 mice). In Exp. 1, the mice were divided into five groups as follows: Aβ-Fc vaccine administration, IgL-Aβ vaccine administration, K-Aβ vaccine administration, empty-vector administration, and no treatment. In Exps. 2–5, the K-Aβ vaccine administration group was excluded from the analysis because of its lower efficacy than other two vaccines. Each group consisted of 4–6 mice. Prophylactic effects were examined in Exps. 1 and 2. Therapeutic effects were examined in Exps. 3 and 4. All APP23 mice were analyzed immunohistochemically with mAb (6F∕3D) against Aβ7-18. Then, the reduction of amyloid plaque was quantified, as shown in Materials and Methods. In Exp. 5, DNA vaccines were administered to B6 mice to know whether the vaccines induce neuroinflammation. Tissues from three mice in each group were immunohistochemically stained with mAbs against CD5 and Mac-3. Neg, negative finding, i.e., no neuroinflammation; N.T., not tested; Exp., experiment; Tx, treatment; Tg, transgenic; Emp, empty vector.