Compositions and methods for inducing immune tolerance
The present invention provides liposomal compositions for inducing immune tolerance. The compounds typically comprise a liposome displaying a specific antigen and also a binding moiety for a sialic acid binding Ig-like lectin (Siglec)expressed on B cells. The invention also provides methods for inducing tolerance to a protein or polypeptide antigen (e.g., a protein antigen) in a subject. The methods involve administering to the subject a pharmaceutical composition that co-presents both the antigen and a glycan ligand for a Siglec expressed on B lymphocytes.
1. A method for reducing antigen-specific antibodies to a polypeptide antigen in a subject, comprising administering to the subject a pharmaceutical composition comprising a liposome; a CD22, Siglec G, or Siglec-10 glycan ligand; and an effective amount of a T cell-dependent MHC class II, B cell-specific polypeptide antigen that is linked to a lipid and co-displayed on the liposome with the CD22, Siglec G, or Siglec-10 glycan ligand; to thereby reduce production of antibodies to the antigen by B cells in the subject.
2. The method of claim 1 , wherein the antigen is an autoantigenan or an alloantigen.
3. The method of claim 1 , wherein the subject is a human.
4. The method of claim 3 , wherein the Siglec ligand is 9-N-biphenylcarboxyl-NeuAcα2-6Galβ1-4GlcNAc (6′-BPCNeuAc), NeuAcα2-6Galβ1-4GlcNAc, or NeuAcα2-6Galβ1-4(6-sulfo)GlcNAc.
5. The method of claim 1 , wherein the polypeptide antigen is a self-antigen, an autoantigen, an alloantigen, a food antigen, or a tissue specific antigen.
6. The method of claim 1 , wherein the polypeptide antigen is a foreign antigen.
7. The method of claim 1 , wherein the administering is parenteral administration.