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

Thanh Loc Nguyen, Youngjin Choi, Jihye Im, Hyunsu Shin, Ngoc Man Phan, Min Kyung Kim, Seung Woo Choi and Jaeyun Kim ()
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Thanh Loc Nguyen: Sungkyunkwan University (SKKU)
Youngjin Choi: Sungkyunkwan University (SKKU)
Jihye Im: Sungkyunkwan University (SKKU)
Hyunsu Shin: Sungkyunkwan University (SKKU)
Ngoc Man Phan: Sungkyunkwan University (SKKU)
Min Kyung Kim: Sungkyunkwan University (SKKU)
Seung Woo Choi: Sungkyunkwan University (SKKU)
Jaeyun Kim: Sungkyunkwan University (SKKU)

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-35263-9

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