Methods and pharmaceutical compositions for inducing immune tolerance by mucosal vaccination with Fc-coupled antigens
The present invention relates to methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.
1. A method for inducing tolerance to a pancreatic beta cell antigen of interest in a subject in need thereof, comprising mucosally administering to the subject a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and a preproinsulin peptide comprising the pancreatic beta cell antigen.
2. The method of claim 1 wherein the pancreatic beta cell antigen is an auto-antigen, an allergen or a molecule that is exogenously administered for therapeutic purposes.
3. The method of claim 1 wherein the subject is an adult, a pregnant woman or a child.
4. The method of claim 1 wherein the subject is a newborn or a neonate.
5. The method of claim 1 wherein the subject is predisposed or believed to be predisposed to developing, or has already developed or is developing diabetes.
6. The method of claim 1 wherein the subject is predisposed or believed to be predisposed to developing, or has already developed or is developing an immune response to an insulin antigen expressed by pancreatic beta cells.
7. The method of claim 1 wherein the subject is predisposed or believed to be predisposed to developing, or has already developed or is developing an immune reaction against insulin that is exogenously administered for therapeutic or other purposes.
8. The method of claim 1 wherein the FcRn targeting moiety is an Fc of an IgG antibody or a portion of the Fc.
9. The method of claim 1 wherein the recombinant chimeric construct is a fusion protein that comprises an amino acid sequence comprising a portion of an Fc region and an amino acid sequence encoding the preproinsulin peptide.
10. The method of claim 1 wherein the recombinant chimeric construct is administered to the subject by administering recombinant bacteria that express the construct.
11. The method of claim 1 wherein the recombinant chimeric construct is delivered via the oral cavity.
12. The method of claim 1 wherein the recombinant chimeric construct is delivered via the respiratory tract.
13. The method of claim 8 , wherein the IgG antibody is an IgG1 antibody or an IgG4 antibody.