Table 3.
Particle-based tolerogenic vaccines.
| Nano and Microparticle Tolerogenic Vaccines | Prophylactic Treatment | Therapeutic Treatment | Bystander/Infectious Tolerance | Proposed Mechanism of Action | Ref | ||||
|---|---|---|---|---|---|---|---|---|---|
| Route | Days | EAE Model | Route | Days | EAE Model | ||||
| 400-500 nm PS or PLG NP bearing PLP139-151 |
IV | -7 | SJL with PLP139-151 |
IV | 11 or 18 | SJL with PLP139-151 |
Yes | Antigen targeting to marginal zone macrophages in the spleen led to effector T cell apoptosis and anergy. Tolerance was dependent on vaccine induced Tregs and IL-10. SC vaccination was ineffective. NP bearing PLP139-151 mediated infectious tolerance to PLP178-191-induced EAE in SJL mice. | (164) |
| 170-220 nm PLGA NP encapsulating PLP139-191 and rapamycin |
IV | -21 and -14 | Hemophilia A mice with PLP139-151 | IV or SC | 13 or 14 | SJL with PLP139-191 |
N/A | Antigen targeting to marginal zone macrophages in the spleen and myeloid APCs in the lymph nodes with rapamycin to modulate local immune environment, inhibited antigen-specific T cell proliferation and induced antigen-specific tetramer+ Tregs in spleen of vaccinated mice. Tregs from vaccinated mice transferred tolerance to naïve recipient mice. | (165, 166) |
| 700-900 nm PLG NP encapsulating PLP139-151 with tethered TGF-β |
IV or SC | -7 | SJL with PLP139-151 |
IV | 13 | SJL with PLP139-151 |
N/A | Antigen delivery with TGF-β to modulate local immune environment resulted in decreased DC production of IL-6 and IL-12 and increased the number of polyclonal Tregs in the liver of mice. | (167) |
| 3.5-4.5 µm PLGA MPs loaded with MOG35-55 and rapamycin |
NA | NA | NA | ILN | 10 or 16 | C57BL/6 with MOG35-55 | N/A | Antigen delivery to lymph node with rapamycin to modulate local immune environment increased polyclonal Tregs in CNS, lymph nodes, and spleen, reduced IFN-γ and IL-17 responses and decrease lymphocyte infiltration into CNS. | (168) |
| 20 nm Quantum dots bearing MOG35-55 |
SC | 2 | C57BL/6 with MOG35-55 | NA | NA | NA | N/A | Antigen delivery to MARCO+ macrophages in lymph nodes increased polyclonal Tregs in the draining lymph nodes. Tolerance was dependent on NP antigen loading density. | (169) |
| 10-20 nm Poly(maleic anhydride-alt-1-octadecene) coated iron oxide nanocrystals loaded with MOG35-55 or MBP1-9 |
IV | 1 | C57BL/6 with MOG35-55 or B10.PL or Tg4 with MBP1-9 | IV | Administered at disease onset | C57BL/6 with MOG35-55 | N/A | Antigen targeting to LSECs increased the percentage of polyclonal Tregs in the spleen. Tolerance was dependent on vaccine-induced Tregs. | (170) |
| 60 nm Gold particles loaded with PEG, ITE, and MOG35-55 or PLP139-151 |
IP | -30, -29 and -28 or -16, -15 and -14 or -9, -8 and -7 or -3, -2 and -1 | C57BL/6 with MOG35-55 | IP | 17, 24,31, 38 and 45 or 7 or 14 or 35 | SJL with PLP139-151, C57BL/6 with MOG35-55, or NOD with MOG35-55 |
Yes | Antigen targeting to DCs with ITE to modulate local immune environment induced tolerogenic DCs and increased polyclonal Tregs in the spleen of vaccinated mice. Tregs from vaccinated mice transferred tolerance to naïve recipient mice. NP carrying ITE and MOG35-55 suppressed EAE induced with PLP139-151 in SJL x C57BL/6 F1 mice. | (171, 172) |
| 40-50 nm Dextran coated or pegylated iron oxide NPs coated with MHCII loaded with MOG38-49, MOG97-108 or PLP175-192 |
N/A | N/A | N/A | IV or SC | 14 or 21 and weekly | C57BL/6 with MOG35-55 or C57BL/6 IAbnull HLA-DR4-IE Tg mice with PLP175–192 |
Yes | Antigen presenting NPs induced Tr1 cells from memory experienced populations. NP carrying MOG97-108 suppressed PLP175-192 induced EAE. Likewise, NP bearing ubiquitous PDC or CYP2D6 peptide-MHCII complexes suppressed EAE. | (173, 174) |
| 180-260 nm PLGA NP bearing MOG40–54/H-2Db-Ig dimer, MOG35–55/I-Ab multimer, anti-Fas, PD-L1-Fc and CD47-Fc |
NA | NA | NA | IV | 8, 18, 28 and 38 | C57BL/6 MOG35-55 | N/A | Antigen presenting NP with immunoregulatory molecules to modulate the local immune environment decreased MOG35–55-reactive Th1 and Th17 cells, increased regulatory T cells, inhibited T cell proliferation and elevated T cell apoptosis in spleen. | (175) |
| 60-90 nm Mannosylated liposomes loaded with MBP46–62, MBP124–139, or MBP147–170 or combination | N/A | N/A | N/A | SC | 7, 8, 9, 10, 11 and 12 | Dark Agouti Rats MBP63-81 |
Yes | Antigen targeting to CD206+ DCs resulted in decrease anti-MBP autoantibodies and down-regulate Th1 cytokine profile in the CNS. NP carrying MBP46–62, MBP124–139, or MBP147–170 prevented MBP63-81 induced EAE in Dark Agouti rats. | (176) |