Table 2.
Peptide-based Aβ-, tau-, and α-syn vaccines for neurodegenerative diseases: Animal models, vaccination schemes and methods for evaluating efficacy reported in recent preclinical studies.
| Target | Peptide Epitope | Animal Model | Vaccination Scheme (Administration Route/Doses/Time Intervals) | Methods for Evaluating Vaccination Efficacy | Reference |
|---|---|---|---|---|---|
| Aβ | Aβ(1-6) | C57/BL6 mice | i.m. 1/x4/2 w intervals | In vitro: ELISA; ELISpot; MTT 2 assay | [74] |
| Aβ | Aβ(1-6) | C57/BL6 mice | i.m./x4/2 w intervals | In vitro: ELISA; ELISpot | [73] |
| Aβ | Aβ(3-10) | APPSwe/PSEN1dE9- mice | s.c. 1/x6/ 2 w intervals |
In vitro: ELISA; immunohistochemistry; Western Blot; TUNEL 3 staining; ROS 4 staining | [72] |
| Aβ | Aβ(3-10) | 3xTg-AD mice | s.c./x7/2 w or 4 w intervals | In vitro: ELISA; immunohistochemistry; Western Blot In vivo: MWM test |
[70] |
| Aβ | Aβ(3-10) | APP/PS1 mice | s.c./x5/ 2 w or 4 w inter-vals |
In vitro: ELISA; immunohistochemistry In vivo: MWM test |
[71] |
| Aβ | Aβ(1-11) | 3xTg-AD mice | s.c./x3/4 m or 5 m intervals | In vitro: ELISA; immunohistochemistry; Thioflavin S staining | [80] |
| Aβ | Aβ(1-11) DNA vaccine |
Tg2576 mice Tg-SwDI mice |
i.d. 1/x4/ 2 w or 4 w intervals |
In vitro: ELISA; immunohistochemistry In vivo: MRI5 imaging |
[79] |
| Aβ | Aβ(1-15) | APP/PS1 mice | s.c./x3/ 2 w intervals |
In vitro: ELISA; immunohistochemistry; Western Blot In vivo: Spontaneous Y maze test; NOR 6 test; MWM 7 test |
[77] |
| Aβ | Aβ(1-15) | APPSwe/PSEN1dE9- mice | Orally/every day for ~9 months | In vitro: ELISA; Immunohistochemistry In vivo: water maze test |
[76] |
| Aβ | Aβ(1-6), Aβ(1-15) | Balb/C mice | s.c./x4/2 w intervals | In vitro: ELISA; Dot Blot; Thioflavin T staining; TEM 8 scanning | [75] |
| Aβ | cyclo[Aβ(22-28)-Y9NGK’], cyclo[Aβ(23-29)- YNGK’], cyclo[Aβ(22-29)- YNGK’] |
J20 | s.c./x3/1 m intervals | In vitro: ELISA; immunohistochemistry In vivo: OF 10 test; SA 11 test; NOR test; NLR 12 test; MWM test |
[81] |
| Aβ | Oligomer-specific Aβ mimotope peptide | EAE/AD mice | s.c./x5/2 w intervals | In vitro: ELISA; Immunohistochemistry In vivo: MWM test; Y maze test; NOR test |
[84] |
| Aβ | Aβ(1-42) | 3xTg-AD mice or Neuroinflammation model in C57/BL6 |
s.c./x6/2 w intervals | In vitro: ELISA; immunohistochemistry; Flow cytometry In vivo: MWM test; PET 13 scanning |
[82] |
| Aβ | Aβ(1-42) DNA vaccine |
3xTg-AD mice | i.d./x13/ 2 w or 6 w intervals |
In vitro: ELISA; ELISpot; immunohistochemistry; Western Blot | [83] |
| Aβ, Tau | Aβ(1–11), Tau(2–18) | Tau22/5xFAD bigenic mice (T5x) | i.m./x4/1 m or 1.5 m intervals |
In vitro: ELISA; immunohistochemistry; Western Blot; SPR 14 biosensor | [78] |
| Aβ, Tau | Linear Aβ(1-6), Aβ(1-6)3, Aβ(1-15), Tau(294-305), p 15Tau(396-404), pTau422 cycloAβ(1-7), cycloEP1 16, cycloEP2 16 |
BALB/c mice and TauP301S mice |
s.c. 3 times at 2 w intervals s.c. 4 times at 2 w intervals |
In vitro: ELISA; immunohistochemistry In vivo: Forced Y maze test; NOR test; MWM test |
[40] |
| Tau | Tau(2-18) | Tg4510 mice | i.m./x7/2 w or 4 w intervals | In vitro: ELISA; ELISpot; immunohistochemistry; Western blot In vivo: NOR test; RAWM 17 test |
[34] |
| Tau | Tau(2-18) | PS19 mice | i.m./x4 times/1 m, 1.5 m, or 2.5 m intervals | In vitro: ELISA; immunohistochemistry; Western blot, Dot Blot, confocal microscopy In vivo: Rotarod test; Y-maze test; NOR test; NPR 18 test |
[92] |
| Tau | Tau(294-305) | TauP301S mice | s.c./x4/2 w or 3 w intervals | In vitro: ELISA; immunohistochemistry; Western blot In vivo: Forced Y maze test; Spontaneous Y maze test; NOR test; MWM test |
[94] |
| Tau | Tau(175-190)[p181] | Tg4510 mice | i.m./x3 times/2 w intervals | In vitro: ELISA; immunohistochemistry; Western blot In vivo: NOR test; MWM test |
[96] |
| Tau | Tau(195-213) [p 15202/205]; Tau(207-220) [p212/214]; Tau(224-238) [p231] | APPSwe/PSEN1dE9 mice | s.c./x2/1 w interval | In vitro: ELISA; immunohistochemistry; immunoblot In vivo: T maze test; MWM test; EAE 19 score |
[95] |
| Tau | Tau(379-408) [p396/404] | 3xTg-AD mice | s.c./x4/2 w or 4 w intervals | In vitro: ELISA; immunohistochemistry; Western blot In vivo: Rotarod test; RAWM test; close field symmetrical maze; locomotor activity; traverse beam test |
[100] |
| Tau | pTau30 [p202/205/238/262], pTau31 [p202/205/396/404], pTau35 [p238/262/396/404] | TauP301S mice | -/x4/- | In vitro: ELISA; ELISpot; immunohistochemistry In vivo: Rotarod test; hind-limb clasping test; grip strength test; kyphosis test |
[97] |
| α-Syn | α-Syn(85-99) α-Syn(109-126) α-Syn(126-140) |
B6SJL mice | s.c./x4/2 w interval | In vitro: ELISA; ELISpot; immunohistochemistry; Western blot | [111] |
| α-Syn | middle region: C9GGKNEEGAPQ (PD1) N-terminal: MDVFMKGLGGC (PD2) C-terminal: CGGEGYQDYEPEA (PD3) |
SNCA-OVX mice | s.c./x3, x4, x5, x14/2 w or 4 w intervals | In vitro: ELISA; immuno-histochemistry; Western blot; AS-PLA 20 In vivo: Rotarod test; locomotor activity; digitized gait assessment; inverted screen test |
[43] |
1 i.m./s.c./i.d.: intramuscular/subcutaneous/intradermal route of administration. 2 MTT: 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide. 3 TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling. 4 ROS: Reactive oxygen species. 5 MRI: Magnetic resonance imaging. 6 NOR: Novel object recognition. 7 MWM: Morris water maze. 8 TEM: Transmission electron microscopy. 9 Amino acids shown with the one-letter code. 10 OF: Open field. 11 SA: Spontaneous alternation. 12 NLR: Novel location recognition. 13 PET: Positron emission tomography. 14 SPR: Surface plasmon resonance. 15 p: Phosphorylated amino acid residue(s) at a specific site in the protein sequence. 16 EP1, EP2: Special peptide epitopes of Aβ oligomers selected with phage display from random peptide libraries. 17 RAWM: Radial arm water maze. 18 NPR: Novel placement recognition. 19 EAE: Experimental autoimmune encephalomyelitis. 20 AS-PLA: Alpha-synuclein proximity ligation assay.