Adjuvants as Delivery Systems in Antigen-Specific Immunotherapies

Combining autoantigens with immune-modulating drugs has emerged as an attractive approach to selectively reinstate tolerance in autoimmune diseases. The disparate properties of autoantigens and small-molecule immunosuppressants commonly used to treat autoimmune diseases can confound efforts to co-deliver these therapies. However, both components may be co-delivered with adjuvants which have been successful in delivering antigens to immune cells. We evaluated several common adjuvants as vehicles to co-deliver a model antigen and immunosuppressant, ovalbumin (OVA) and dexamethasone (DEX), respectively. Formulations were developed, and the release of DEX from adjuvants was investigated. Next, the effect of adjuvant, DEX, and OVA was tested in vitro using a DC line. A MF59-analog (MF59a) formulation was advanced to more sophisticated co-culture studies using OVA-primed bone marrow-derived dendritic cells and splenocytes or T-cells from OT-II mice. Most of these studies indicated MF59a-based antigen-specific immunotherapies could diminish the markers of inflammation associated with OVA recognition. We rationalized MF59a co-delivery of antigen and drug could reduce the risk of side effects typically associated with these drugs and reinstate immune tolerance, thus prompting continued investigation of emulsion adjuvants as delivery vehicles for antigen-specific immunotherapy of autoimmune diseases.