TY - JOUR
T1 - Tocopherol Emulsions as Functional Autoantigen Delivery Vehicles Evoke Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis
AU - Griffin, J. Daniel
AU - Christopher, Matthew A.
AU - Thati, Sharadvi
AU - Salash, Jean R.
AU - Pressnall, Melissa M.
AU - Weerasekara, Dhanushka B.
AU - Lunte, Susan M.
AU - Berkland, Cory J.
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/2/4
Y1 - 2019/2/4
N2 - 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 (PLP 139-151 ) 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 PLP 139-151 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.
AB - 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 (PLP 139-151 ) 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 PLP 139-151 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.
KW - antigen-specific immunotherapy
KW - antioxidant
KW - codelivery
KW - experimental autoimmune encephalomyelitis (EAE)
KW - proteolipid protein (PLP )
KW - tocopherol
UR - https://www.scopus.com/pages/publications/85060275560
U2 - 10.1021/acs.molpharmaceut.8b00887
DO - 10.1021/acs.molpharmaceut.8b00887
M3 - Article
C2 - 30615457
AN - SCOPUS:85060275560
SN - 1543-8384
VL - 16
SP - 607
EP - 617
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 2
ER -