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Tocopherol Emulsions as Functional Autoantigen Delivery Vehicles Evoke Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis
Griffin, J. Daniel Christopher, Matthew A. Thati, Sharadvi Salash, Jean Remy Pressnall, Melissa M. Weerasekara, Dhanushka B. Lunte, Susan M. Berkland, Cory J.
Griffin, J. Daniel
Christopher, Matthew A.
Thati, Sharadvi
Salash, Jean Remy
Pressnall, Melissa M.
Weerasekara, Dhanushka B.
Lunte, Susan M.
Berkland, Cory J.
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Abstract
Contemporary approaches to treating autoimmune diseases like multiple sclerosis broadly modulate the immune system and leave patients susceptible to severe adverse effects. Antigen-specific immunotherapies (ASIT) offer a unique opportunity to selectively suppress autoreactive cell populations but have suffered from marginal efficacy even when employing traditional adjuvants to improve delivery. The development of immunologically active antigen delivery vehicles could potentially increase the clinical success of antigen-specific immunotherapies. An emulsion of the antioxidant tocopherol delivering an epitope of proteolipid protein autoantigen (PLP139–151) yielded significant efficacy in mice with experimental autoimmune encephalomyelitis (EAE). In vitro studies indicated tocopherol emulsions reduced oxidative stress in antigen-presenting cells. Ex vivo analysis revealed that tocopherol emulsions shifted cytokine responses in EAE splenocytes. In addition, IgG responses against PLP139–151 were increased in mice treated with tocopherol emulsions delivering the antigen, suggesting a possible skew in immunity. Overall, tocopherol emulsions provide a functional delivery vehicle for ASIT capable of ameliorating autoimmunity in a murine model.
Description
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.molpharmaceut.8b00887.
Date
2019-01-07
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American Chemical Society
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Keywords
Antigen-specific immunotherapy, Experimental autoimmune encephalomyelitis (EAE), Codelivery, Antioxidant, Tocopherol, Proteolipid protein (PLP139−151)
Citation
Griffin, J. D., Christopher, M. A., Thati, S., Salash, J. R., Pressnall, M. M., Weerasekara, D. B., … Berkland, C. J. (2019). Tocopherol Emulsions as Functional Autoantigen Delivery Vehicles Evoke Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis. Molecular pharmaceutics, 16(2), 607–617. doi:10.1021/acs.molpharmaceut.8b00887