Immunosuppressive biomaterial-based therapeutic vaccine to treat multiple sclerosis via re-establishing immune tolerance

• Published in: Nature communications Vol. 13; no. 1; p. 7449
• Main Authors: Nguyen, Thanh Loc, Choi, Youngjin, Im, Jihye, Shin, Hyunsu, Phan, Ngoc Man, Kim, Min Kyung, Choi, Seung Woo, Kim, Jaeyun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 147/143; 631/250/1619/554/1898/1271; 631/250/24/1313; 631/61/54/1866; 692/699/375/1666; Animals; Antigen-presenting cells; Antigens; Autoantigens; Autoimmune diseases; Biocompatible Materials; Biomaterials; Biomedical materials; CD4 antigen; Central nervous system; Cerium; Cerium oxides; Encephalomyelitis, Autoimmune, Experimental - therapy; Experimental allergic encephalomyelitis; Foxp3 protein; Humanities and Social Sciences; Humans; Immune system; Immune Tolerance; Immunization; Immunological tolerance; Immunosuppressive Agents; Introduced species; Lymphocytes T; Mice; multidisciplinary; Multiple sclerosis; Multiple Sclerosis - therapy; Nanoparticles; Oxygen; Paralysis; Reactive Oxygen Species; Scavenging; Science; Science (multidisciplinary); Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35263-9

Current therapies for autoimmune diseases, such as multiple sclerosis (MS), induce broad suppression of the immune system, potentially promoting opportunistic infections. Here, we report an immunosuppressive biomaterial-based therapeutic vaccine carrying self-antigen and tolerance-inducing inorganic nanoparticles to treat experimental autoimmune encephalomyelitis (EAE), a mouse model mimicking human MS. Immunization with self-antigen-loaded mesoporous nanoparticles generates Foxp3 + regulatory T-cells in spleen and systemic immune tolerance in EAE mice, reducing central nervous system-infiltrating antigen-presenting cells (APCs) and autoreactive CD4 + T-cells. Introducing reactive oxygen species (ROS)-scavenging cerium oxide nanoparticles (CeNP) to self-antigen-loaded nanovaccine additionally suppresses activation of APCs and enhances antigen-specific immune tolerance, inducing recovery in mice from complete paralysis at the late, chronic stage of EAE, which shows similarity to chronic human MS. This study clearly shows that the ROS-scavenging capability of catalytic inorganic nanoparticles could be utilized to enhance tolerogenic features in APCs, leading to antigen-specific immune tolerance, which could be exploited in treating MS. Multiple sclerosis is a debilitating autoimmune disease, for which therapy is not curative, only slowing down progression at the expense of general immune suppression. Here authors show that in a mouse model of multiple sclerosis, disease progression could be halted or even reversed by a nanovaccine, composed of reactive oxygen species scavenging cerium oxide nanoparticles, which establishes immune tolerance against the relevant autoantigen.