Contributions
Abstract: EP1638
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Currently approved therapeutics for Multiple Sclerosis compromise the entire immune system, leading to a susceptibility to severe side effects such as opportunistic infections. Co-delivery applications of antigens with immunomodulatory drugs have shown unique potential to overcome global immunosuppression through their ability to skew immunity with antigen-specificity. Historically, the necessity of a spatially associative vehicle has been viewed as a setback to co-delivery approaches due to factors such as the immunogenicity of nanoparticles or clinical incompatibility of Freund's adjuvants. Development of a functional vehicle capable of substantially contributing to desired tolerogenic outcomes would be of great value in the advancement of co-delivered antigen-specific immunotherapies (ASITs). In this work, antioxidant tocopherol-based emulsions were selected and evaluated for their functional utility as ASIT vehicles. 4-5 week old SJL/J female mice were induced with experimental autoimmune encephalomyelitis (EAE) and treated with either PBS, tocopherol emulsion alone (ETPGS), or tocopherol emulsion plus 200 nmol PLP139-151 (ETPGS+PLP, n=3/group) on days 4, 7 and 10. Mice treated with ETPGS alone exhibited a delayed clinical onset, but fully severe disease while ETPGS+PLP-treated mice showed an even further delayed onset with significantly suppressed symptoms. On day 25, splenocytes were harvested and incubated with and without 25µM PLP rechallenge for 120 hours. Following the incubation period, a multiplexed cytokine panel, ELISPOT and flow cytometry were conducted. Significantly increased Il-10 (p< 0.01) and Il-4 (p< 0.05) were observed in the ETPGS+PLP group over both the PBS vehicle and ETPGS alone, suggesting antigen-specific tolerance. These data, when combined with the clinical effectiveness of ETPGS+PLP show that tocopherol vehicles can serve as potent antigen delivery systems. Further investigation of these formulations may elucidate their utility as functional co-delivery vessels for autoimmune applications.
Disclosure: The authors declare no conflict of interest regarding the works presented herein, though with gracious appreciation we thank the Madison and Lila Self Graduate Fellowship of the University of Kansas for funding J. D. Griffin.
Abstract: EP1638
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Currently approved therapeutics for Multiple Sclerosis compromise the entire immune system, leading to a susceptibility to severe side effects such as opportunistic infections. Co-delivery applications of antigens with immunomodulatory drugs have shown unique potential to overcome global immunosuppression through their ability to skew immunity with antigen-specificity. Historically, the necessity of a spatially associative vehicle has been viewed as a setback to co-delivery approaches due to factors such as the immunogenicity of nanoparticles or clinical incompatibility of Freund's adjuvants. Development of a functional vehicle capable of substantially contributing to desired tolerogenic outcomes would be of great value in the advancement of co-delivered antigen-specific immunotherapies (ASITs). In this work, antioxidant tocopherol-based emulsions were selected and evaluated for their functional utility as ASIT vehicles. 4-5 week old SJL/J female mice were induced with experimental autoimmune encephalomyelitis (EAE) and treated with either PBS, tocopherol emulsion alone (ETPGS), or tocopherol emulsion plus 200 nmol PLP139-151 (ETPGS+PLP, n=3/group) on days 4, 7 and 10. Mice treated with ETPGS alone exhibited a delayed clinical onset, but fully severe disease while ETPGS+PLP-treated mice showed an even further delayed onset with significantly suppressed symptoms. On day 25, splenocytes were harvested and incubated with and without 25µM PLP rechallenge for 120 hours. Following the incubation period, a multiplexed cytokine panel, ELISPOT and flow cytometry were conducted. Significantly increased Il-10 (p< 0.01) and Il-4 (p< 0.05) were observed in the ETPGS+PLP group over both the PBS vehicle and ETPGS alone, suggesting antigen-specific tolerance. These data, when combined with the clinical effectiveness of ETPGS+PLP show that tocopherol vehicles can serve as potent antigen delivery systems. Further investigation of these formulations may elucidate their utility as functional co-delivery vessels for autoimmune applications.
Disclosure: The authors declare no conflict of interest regarding the works presented herein, though with gracious appreciation we thank the Madison and Lila Self Graduate Fellowship of the University of Kansas for funding J. D. Griffin.