Fusion of Antigen with Efferocytic Mediators Induces Antigen-Specific Tolerance and Reduces Allergic Airway Inflammation in Mice

We made proteins that combine efferocytic mediators, which help clear dying cells, and ovalbumin (OVA), a model antigen. We demonstrate that these fusions maintain affinity to their membrane target, phosphatidylserine, and enhance uptake by murine dendritic cells in vitro. Furthermore, we found that antigen-pulsed DCs were capable of driving proliferation of both cognate CD4+ and CD8+ T cells, demonstrating evidence of antigen degradation and presentation. Similar observations were made following adoptive transfer of OVA-specific T cells into naive mice, in which the T cells demonstrated dampened recovery and effector function. Finally, we explored GAS6-OVA, one of the biologics described in this work, in the context of an allergic airway inflammation model in mice. After being treated prophylactically with GAS6-OVA, mice demonstrated lesser eosinophilia in bronchealveolar lavage fluid and lesser mucus hypersecretion as assessed by histology following challenge with OVA. These results suggest that our proteins can induce tolerance to a specific antigen, which may be useful for diseases caused by an abnormal immune response to a known antigen. Future work will explore the potential of our proteins to treat these diseases, to induce tolerance to other antigens, and to modulate immune responses in the context of an antigen-experience immune system.