Table 3.
Comparative analysis of in vivo immunotherapeutic investigations of prion diseases.
In vivo | ||||
---|---|---|---|---|
Treatment | Region | Model | Efficacy | Reference |
Passive | scFv 8H4 (145–180) | Lysates from scFv PC12 cells i.c. injected into mice 35 days after scrapie exposure | 2/10 mice protected from 8/10 infection mice symptom-free after 300 days | Vetrugno et al. 2005 [183] |
| ||||
Passive | Anti-PrP IgG Abs ICSM 35 (94–105) ICSM 18 (144–152) |
Mice challenged i.p. with scrapie, Ab treatment twice weekly | Signficant delay in prion symptoms. Reduction in splenic PrPsc and delayed transfer to brain | White et al. 2003 [184] |
| ||||
Passive | mAb 8B4 (34–52) mAb 8H4 (175–185) 8F9 (205–233) |
Mice challenged i.p. with scrapie, weekly treatment with Ab | 8H4 and 8B4 10% longer incubation period at high challenge dose. At low challenge dose, 8B4 prevented disease in 10% of animals | Sigurdsson et al. 2003 [185] |
| ||||
Passive (engineered) | Transgenic mice expressing 6H4 (144–152) as single chain-Ab | Mice challenged i.p. with scrapie | Prolonged survival by 120 days | Heppner et al. 2001 [186] |
| ||||
Passive (engineered) | PrPC
specific scFv |
Expression specifically in CNS with recombinant adenoassociated vector type 2 viral vector platform | Delayed onset in peripherally inoculated mice | Wuertzer et al. 2008 [187] |
| ||||
Active | rPrPC
23–230 |
s.c. vaccination of mice | 10% increase in incubation time; correlated with Ab titres | Sigurdsson et al. 2003 [188] |
| ||||
Active | Peptide 105–125 rPrPC 90–230 | Mice immunized and orally challenged with infected brain homogenate | Peptide improved survival by 23 days; protein had no effect | Schwarz et al. 2003 [189] |
| ||||
Active (engineered) | Human PrPC | Transfer of adenotransduced dendritic cells. Mice challenged i.p. | Prolonged survival times | Rosset et al. 2009 [190] |
| ||||
Active (mucosal) | Salmonella expressing PrP | Four oral vaccinations with live salmonella; 2 with dead Challenge via oral lavage |
100% of mice expressing high IgA and IgG and 33% of mice with high-IgG and low-IgA symptom-free after 400 days | Goñi et al. 2008 [191] |