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Pulmonary Administration of Soluble Antigen Arrays is Superior to Antigen in Treatment of Experimental Autoimmune Encephalomyelitis

Kuehl, C;Thati, S;Sullivan, B;Sestak, J;Thompson, M;Siahaan, T;Berkland, C;

Antigen-specific immunotherapy (ASIT) has been used to hyposensitize patients to allergens and offers an enticing approach for attenuating autoimmune diseases. Applying ASIT to mucosal surfaces such as the lungs may engage unique immune response pathways to improve efficacy. Pulmonary delivery of soluble antigen arrays (SAgAs) was explored in mice with experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. SAgAs were designed to impede immune response to autoantigen epitopes and are composed of a hyaluronan backbone with peptides PLP139-151 and LABL, a disease-causing proteolipid peptide epitope and an ICAM-1 ligand, respectively. Pulmonary instillation of SAgAs decreased disease score, improved weight gain, and decreased incidence of disease in EAE mice compared to pulmonary delivery of HA polymer, LABL, or PLP. Interestingly, treating with PLP alone also showed some improvement. Splenocytes from SAgA-treated animals showed increased IFN- levels, and IL-6 and IL-17 were elevated in SAgA-treated animals compared to PLP treatments. IL-10, IL-2, and TNF- levels showed no significant difference, yet trends across all cytokines suggested SAgAs induced a very different immune response compared to treatment with PLP alone. This work suggests that co-delivery of peptide components is essential when treating EAE via pulmonary instillation, and the immune response may have shifted towards immune tolerance.