Methods and pharmaceutical compositions for inducing immune tolerance by mucosal vaccination with fc-coupled antigens

Abstract

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 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. 
     
     
         2 . The method of  claim 1  wherein the antigen is an auto-antigen, the antigen is an allergen or the antigen is 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 an autoimmune disease. 
     
     
         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 allergy. 
     
     
         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 molecules that are exogenously administered for therapeutic or other purposes. 
     
     
         8 . 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 a grafted tissue or grafted hematopoietic cells or grafted blood cells. 
     
     
         9 . The method of  claim 1  wherein the FcRn targeting moiety is an Fc of an IgG antibody, preferably of an IgG1 or IgG4 antibody, even more preferably of an IgG1 antibody, or a portion of the Fc. 
     
     
         10 . The method of  claim 1  wherein the recombinant chimeric construct of the present invention is a fusion protein that comprises an amino acid sequence consisting of a portion of an Fc region and an amino acid sequence that comprises the antigenic portion of the antigen. 
     
     
         11 . The method of  claim 1  wherein the recombinant chimeric construct is administered to the subject with the means of recombinant bacteria that express the construct. 
     
     
         12 . The method of  claim 1  wherein the recombinant chimeric construct is delivered via the oral cavity. 
     
     
         13 . The method of  claim 1  wherein the recombinant chimeric construct is delivered via the respiratory tract. 
     
     
         14 . The method of  claim 13 , wherein the recombinant chimeric construct is delivered via the nasal cavity.