Tolerogenic Nanovaccine for Prevention and Treatment of Autoimmune Encephalomyelitis

Abstract

Herein, a tolerogenic nanovaccine is developed and tested on an animal model of multiple sclerosis. The nanovaccine is constructed to deliver the self‐antigen, myelin oligodendrocyte glycoprotein (MOG) peptide, and dexamethasone on an abatacept‐modified polydopamine core nanoparticle (AbaLDPN‐MOG). AbaLDPN‐MOG can target dendritic cells and undergo endocytosis followed by trafficking to lysosomes. AbaLDPN‐MOG blocks the interaction between CD80/CD86 and CD28 in antigen‐presenting cells and T cells, leading to decreased interferon gamma secretion. The subcutaneous administration of AbaLDPN‐MOG to mice yields significant biodistribution to lymph nodes and, in experimental‐autoimmune encephalomyelitis (EAE) model mice, increases the integrity of the myelin basic sheath and minimizes the infiltration of immune cells. EAE mice are treated with AbaLDPN‐MOG before or after injection of the autoantigen, MOG. Preimmunization of AbaLDPN‐MOG before the injection of MOG completely blocks the development of clinical symptoms. Early treatment with AbaLDPN‐MOG at three days after injection of MOG also completely blocks the development of symptoms. Notably, treatment of EAE symptom‐developed mice with AbaLDPN‐MOG significantly alleviates the symptoms, indicating that the nanovaccine has therapeutic effects. Although AbaLDPN is used for MOG peptide delivery in the EAE model, the concept of AbaLDPN can be widely applied for the prevention and alleviation of other autoimmune diseases.

Regulation of Antigen‐Specific Immunotherapy with Nanomaterials

“…Oh et al recently designed a tolerogenic nanovaccine for Treg production to suppress autoreactive T cells during MS treatment. [33] Specifically, polydopamine nanoparticles were coated with PEGylated lipids, and the anti-inflammatory drug, Dexamethasone was incorporated into the hydrophobic lipid layer (denoted as LDPN, Figure 3a). LDPN was then conjugated with self-antigen MOG and Abatacept (denoted as AbaLDPN-MOG), wherein Abatacept is a clinically approved IgG1 protein fused with cytotoxic T-lymphocyte antigen 4 (CTLA-4) to treat arthritis.…”

“…DNA/mRNA vaccines can elicit balanced antibody and cytotoxic T lymphocyte responses. Although nucleic acids are easily degraded in vivo and [33] Copyright 2022, Wiley-VCH GmbH. d) A schematic illustrating the mechanism of immunosuppressive therapeutic nanovaccine, MSN-MOG-Ce for the treatment of EAE by generating antigen-specific immunotolerance.…”

“…c) The fractions of MOG-specific Tregs in total CD4 þ Foxp3 þ Treg cells in mice immunized with different vaccine formulations, as indicated. Reproduced with permission [33]. Copyright 2022, Wiley-VCH GmbH.…”

Autoantigenic Peptide and Immunomodulator Codelivery System for Rheumatoid Arthritis Treatment by Reestablishing Immune Tolerance

“…16 For example, codelivery of MOG peptide with an immunomodulator (dexamethasone or rapamycin) remarkably decreased the quantity of CD4 + T cells to restore immune tolerance and relieved the symptoms of multiple sclerosis model mice compared to a single dose of MOG peptide or immunomodulator. 17,18 Therefore, we speculated that combining with autoantigenic peptides and immunomodulators may be a promising strategy for RA treatment by enhancing immune tolerance. About 20−50% of RA patients have type II collagen (CII) antibody in their serum, suggesting that CII plays a key role in promoting the onset of RA, such as attacking and destroying cartilage tissue.…”

ROS-Scavenging Lignin-Based Tolerogenic Nanoparticle Vaccine for Treatment of Multiple Sclerosis

“…Recently, nano- and microparticles have been explored as potential carriers for delivering self-antigens and tolerogenic cues to investigate their potential in the treatment of autoimmune diseases. For example, different types of nanoparticles, including poly­(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs), − lipid NPs, mesoporous silica NPs, and polydopamine NPs, have been investigated for the treatment of MS. Typically, to create tolerogenic nanovaccines, immunosuppressive agents or immunomodulators like rapamycin, dexamethasone, TGF-β1, and vitamin D3, in addition to autoantigens, are loaded in nanoparticles to induce immune tolerance.…”