Table 4.
DNA-based tolerogenic vaccines.
| DNA/RNA-Based Tolerogenic Vaccines | Prophylactic Treatment | Therapeutic Treatment | Bystander/Infectious Tolerance | Proposed Mechanism of Action | Ref. | ||||
|---|---|---|---|---|---|---|---|---|---|
| Route | Days | EAE Model | Route | Days | EAE Model | ||||
| DNA pCMV full-length MOG or full-length MBP | IM | -28 and -14 | C57BL/6 with MOG35-55 | IM | 10, 24 and 32 | C57BL/6 with MOG35-55 | Yes | Ectopic expression of MOG35-55 in muscle resulted in decreased Th1/Th2 responses, increased FOXP3 mRNA in CNS and increased Tregs in spleen. The DNA vaccine encoding full-length MBP suppressed MOG35-55-induced EAE. | (190) |
| DNA pfascin1 MOG35-55 coadministered with DNA pCMV IL-10 | ID | -21, -14, and -7 | C57BL/6 with MOG35-55 | N/A | N/A | N/A | N/A | Ectopic expression of MOG35-55 in skin resident DCs with IL-10 to modulate the local immune environment reduced IFN-γ and IL-17 producing T cell infiltration in CNS. No detectable increase in Tregs. | (191) |
| DNA liver-specific promoter full-length MOG packaged in AAV coadministered with or without rapamycin | IV | -200 or -14 |
C57BL/6 with MOG35-55 | IV | Treatment administered at Score 1.4, 3.0, or 3.5 | C57BL/6 with MOG35-55 | N/A | Ectopic expression of MOG in liver resulted in increased percentages of MOG35-55 tetramer+ Tregs in spleen, increased polyclonal Tregs in blood and reduced autoantibody production. | (192) |
| DNA pCMV MOG35-55 coadministered with FK506 | IM | -7 | C57BL/6 with MOG35-55 | IM | 3, 7, 17 and 20 | C57BL/6 with MOG35-55 | N/A | Ectopic expression of MOG35-55 and coadministration of FK506 to modulate immune environment resulted in increased Tregs in spleen and spinal cord of vaccinated mice. | (193, 194) |
| DNA pCMV MBP68-86 coadministered DNA pCMV IL-10 | N/A | N/A | N/A | IM | 10 and/or 12 | Lewis Rat with MBP68-86 | Yes | Ectopic expression of MBP68-86 with IL-10 to modulate local immune environment led to the induction of Tr1 cells in lymph nodes. The MBP68-86-DNA with IL-10-DNA vaccine suppressed MBP87-99-induced EAE. | (195) |
| DNA pCMV MOG35-55 coadministered with DNA pCMV TGF-β | ID | -21, -14, and -7 | C57BL/6 with MOG35-55 | N/A | N/A | N/A | N/A | Ectopic expression of MOG35-55 in skin with TGF-β to modulate the local immune environment resulted in reduced IFN-γ and IL-17 producing T cell infiltration into the CNS. No detectable increase in Tregs. | (191) |
| DNA pCMV PLP139-151 or full-length MOG coadministered with DNA pCMV IL-4 | IM | -10 and -17 | SJL with PLP139-151 | IM | 14 and 21 or 18 and 27 | C57BL/6 with MOG35-55 | N/A | Ectopic expression of PLP139-151 with IL-4 to modulate local immune environment reduced the proliferative response of PLP139-151-specific T cells, increased IL-10 and IL-4 and decreased IFN-γ production. Tolerance was transferred from donor to recipient mice via CD4+ (Th2) T cells. | (196) |
| RNA encoding MOG35-55 or PLP139-151 loaded into DC-targeted liposomes (200-400 nm) | N/A | N/A | N/A | N/A | 7 and 10 or when mice reached EAE score of 1-2 | C57BL/6 with MOG35-55 or C57BL/6 x SJL F1 with PLP139-151 or peptide cocktail |
Yes | Ectopic expression of MOG35-55 in DCs decreased the percentage of IFN-γ+ Th1, IL-17+ Th17 T cells, decreased the percentage of MOG35-55-specific CD4+ T cells in the CNS and increased the percentage of MOG35-55-specific Tregs in the spleen of vaccinated mice. The MOG35-55-RNA vaccine prevented PLP139-151 and PLP139-151 or peptide cocktail-induced EAE in C57BL/6 x SJL F1 mice. | (197) |