Multiple antigen glycopeptide carbohydrate vaccine comprising the same and use thereof

Abstract

A carbohydrate peptide conjugate comprising: a carrier comprising a dendrimeric poly-Lysine enabling multiple epitopes to be covalently attachment thereto, at least one peptide comprising one T epitope or several identical or different T epitopes, at least one carbohydrate moiety, or a derivative thereof, containing B epitope provided it is not a sialoside, or several identical or different epitopes. Use of this conjugate for inducing immune response.

What is claimed is:  
     
         1 . A carbohydrate peptide conjugate comprising: 
 a carrier comprising a dendrimeric poly-Lysine enabling multiple epitopes to be covalently attached thereto,    at least one peptide comprising one T epitope or several identical or different T epitopes,    at least one carbohydrate moiety, or a derivative thereof, containing B epitope, provided it is not a slaloside, or several identical or different epitopes.    
     
     
         2 . A conjugate according to  claim 1  wherein said dendrimeric poly-Lysine forms a 4 branches star, with an epitope T covalently bound to each lysine of the branches of said carrier.  
     
     
         3 . A conjugate according to  claim 1  or  2  which comprises at least 3 lysines and up to 15 lysines covalently linked to one another.  
     
     
         4 . A conjugate according to any one of  claims 1  to  3  wherein to the NH2 end of at least two lysine residues is bound at least to one peptide comprising one epitope T and wherein the carbohydrate moiety is covalently bound to the end of said peptide opposite to the lysine.  
     
     
         5 . A conjugate according to any one of  claims 1  to  3  wherein to the NH 2  end of at least two lysine residues is bound at least one carbohydrate residue being not a sialoside, optionally substituted and forming a B epitope and wherein the peptide comprising one T epitope is covalently hound to the end of said-carbohydrate.  
     
     
         6 . A conjugate according to any one of  claims 1  to  5  wherein the carbohydrate moiety is galactosyl.  
     
     
         7 . A conjugate according to any one of  claims 1  to  4  which comprises 3 lysine residues, at least 4 epitopes of the T typo, which may be the same or different, linked to the NH 2  ends of 2 of the lysine residues and 4 α-galactosyl-Nacetyl-Serine residues.  
     
     
         8 . A conjugate according to  claims 1  to  7  wherein the carbohydrate moiety is a galactosyl residue and is substituted by another glycosyl residue.  
     
     
         9 . A conjugate according to  claims 1  to  8  wherein the carbohydrate is a tumor antigen.  
     
     
         10 . A conjugate according to  claims 1  to  9  wherein the epitope T is the 103-115 peptide of the VP1 protein of poliovirus type 1.  
     
     
         11 . A conjugate according to  claims 1  to  10  wherein the carbohydrate is grafted in combination with a tumor peptidic CD8 +  T cell epitope.  
     
     
         12 . A conjugate according to  claims 1  to  8  or  11  wherein the carbohydrate is of bacterial or fungal origin.  
     
     
         13 . A conjugate according to  claim 12  wherein the carbohydrate is from capsular bacterial polysaccharides selected from the group consisting of  Neisseria meningitis, Haemophilus influenza; Streptococcus pneumonia  and other Streptococcus species, with the exception or sialylated polysaccharides.  
     
     
         14 . A conjugate according to  claim 1  wherein the carbohydrate is selected from the group consisting of Tn antigen di-Tn antigen, tri-Tn antigen, T* antigen and hexa-Tn antigen.  
     
     
         15 . A carbohydrate peptide conjugate comprising 
 at least one peptide comprising one T epitope, or several identical or different T epitopes, and    at least one carbohydrate moiety, or a derivative thereof, containing B epitope, provided it is not sialoside, or several identical of different epitopes.    
     
     
         16 . A carbohydrate peptide conjugate according to  claim 15  wherein the carbohydrate moiety is selected from the group consisting of Tn antigen, di-Tn antigen, Tri-Tn antigen, hexa-Tn antigen and T* antigen.  
     
     
         17 . A linear carbohydrate peptide conjugate comprising: 
 at least one peptide comprising one T-epitope, or several identical or different T-epitopes, and    at least one carbohydrate moiety, or a derivative thereof, containing a B-epitope, provided it is not a sialoside.    
     
     
         18 . The linear carbohydrate peptide conjugate of  claim 17 , wherein the peptide and the carbohydrate moiety are directly covalently bound.  
     
     
         19 . The linear carbohydrate peptide conjugate of  claim 17 , wherein the peptide and the carbohydrate moiety are linked via a spacer.  
     
     
         20 . The linear carbohydrate peptide conjugate of  claim 19 , wherein the spacer consists of a aminoacid chain.  
     
     
         21 . The linear carbohydrate peptide conjugate of  claim 19 , wherein the spacer consists of a carbohydrate residue or of a chain of multiple carbohydrate residues.  
     
     
         22 . The linear carbohydrate peptide conjugate of  claim 17 , wherein the carbohydrate moiety is selected from the group consisting of one to six residues of a Tn antigen, a T* antigen or a Tn antigen derivative.  
     
     
         23 . A carbohydrate peptide conjugate comprising: 
 at least one peptide comprising one T epitope or several identical or different T epitopes, wherein at least one T epitope consists of a cytotoxic T cell (CTL) epitope.    
     
     
         24 . A pharmaceutical composition comprising the conjugate according to anyone of  claims 1  to  23  and a suitable carrier.  
     
     
         25 . A pharmaceutical composition comprising the conjugate according to any one  claims 1  to  23  and a suitable carrier and adjuvant.  
     
     
         26 . A vaccine comprising the conjugate according to any one of  claims 1  to  23 .  
     
     
         27 . An immunogenic composition comprising at least one carbohydrate peptide conjugate according to  claims 1  to  23  capable to elect an immune response against a viral infection caused by a pathogen such as hepatitis virus, HIV or CMV.  
     
     
         28 . An immunogenic composition comprising at least one carbohydrate peptide conjugate according to  claims 1  to  23  wherein said composition is capable of increasing the survival of tumour bearing human or animal.  
     
     
         29 . The immunogenic composition comprising at least one carbohydrate peptide conjugate according to  claim 28  wherein said conjugate comprises various carbohydrate antigens to induce more efficient anti-tumour immunity against cancers.  
     
     
         30 . An immunogenic composition comprising a carbohydrate peptide conjugate according to any one of  claims 1  to  22  in combination with a peptide comprising at least one CTL epitope.  
     
     
         31 . An immunogenic composition of Tn molecules capable of enhancing the immune response after coupling said Tn molecule or Tn derivatives on a carrier consisting of a linear peptide or of a dendrimeric peptide or of a protein.  
     
     
         32 . Immunogenic composition of Tn molecules capable of enhancing the immune response after coupling the said Tn or Tn derivatives on a carrier consisting in a linear peptide or a dendrimeric peptide or a protein.  
     
     
         33 . A method of enhancing the immune response of a human or animal body, in particular B and I or T-cell responses, wherein the conjugate according to  claims 1  to  23  is administered to said human or animal body.  
     
     
         34 . A method for enhancing the immune response of a human or animal body in particular B and/or T-cell responses a bacteria wherein the conjugate according to  claim 12  or  13  is administered to said human or animal body.  
     
     
         35 . A method of inducing a B-cell response in a human or animal body, wherein the conjugate according to  claims 1  to  23  is administered to said human or animal body.  
     
     
         36 . Method of vaccination of a human or animal body wherein the conjugate according to  claims 1  to  23  is administered to said human or animal body.  
     
     
         37 . An antibody purified from biological fluid or cells of organisms administered with a conjugate according to  claims 1  to  23 .  
     
     
         38 . A diagnosis kit comprising antigen specific antibodies elicited by immunization of a human or animal body with a conjugate according to  claims 1  to  23 .  
     
     
         39 . A method for the diagnosis of cancer wherein a biological sample is bringing into contact with at least one antibody according to  claim 36  and wherein one determines the formation of complexes between this antibody and molecules comprised in the said sample.  
     
     
         40 . A method for enhancing a T-CD4 +  immune response against an antigen within a human or animal body, wherein the conjugate according to any one of  claims 1  to  23  is administered to said human or animal body.  
     
     
         41 . A method for priming a cytotoxic T cell response in a human or animal body, wherein a conjugate according to  claim 23  comprising at least one CTL epitope is administered to said human or animal body.  
     
     
         42 . A method for priming a cytotoxic T cell response in a human or animal body, wherein an immunogenic composition according to  claim 24  is administered to said human or animal body.