Encapsulating an Immunosuppressant Enhances Tolerance Induction by Siglec-Engaging Tolerogenic Liposomes

Unwanted antibody responses significantly impact human health, and current options for treating deleterious antibody responses largely rely on broad immunosuppressants that can compromise overall immunity. A desirable alternative is to induce antigen-specific immune tolerance. We have shown that co-presentation of antigen and ligands of B cell sialic acid-binding immunoglobulin-like lectins (Siglecs) on a liposomal nanoparticle induces antigen-specific tolerance. Although Siglec-engaging tolerance-inducing antigenic liposomes (STALs) induce robust B cell tolerance in naïve mice, the full potential of STALs requires long-term tolerance induction and suppression of an ongoing immune response. We hypothesized that STALs encapsulated with rapamycin (RAPA), an immunomodulator, could improve the efficacy of STALs and potentially enable their use in the context of immunological memory. Here, we showed that formulation of STALs with RAPA produced enhanced tolerance induction in naïve mice compared to STALs without RAPA but had minimal impact on inducing tolerance in previously sensitized mice. These findings indicate that the addition of immunomodulators to STALs could be beneficial in tolerance induction and support future development of STALs for the treatment of allergy and autoimmune diseases.