Peptide, immunogenic composition and vaccine or medical preparation, a method to immunise animals against the hormone LHRH, and analogs of the LHRH tandem repeat peptide and their use as vaccine

Abstract

The invention relates to a modified tandem LHRH-peptide vaccine preparation in which the amino acid glycine at position (6) of one or both LHRH decapeptides that constitute the tandem unit is substituted by a dextrorotatory amino acid that contains a side chain to which a carrier compound can be coupled. In addition, the tandem LHRH-peptide can be brought into a tandem-dimer form which is also suitable for producing a vaccine that is effective against LHRH (luteinizing hormone releasing hormone), also referred to as GaRH (gonadotropin-releasing hormone), for immunological castration to inhibit or affect reproductive functions or to affect behaviour in vertebrates in general and in domesticated animals and man in particular.

1. A peptide that comprises consisting of at least two contiguous LHRH decapeptide sequences wherein the amino acid glycine at position 6 of at least one of the constituting LHRH decapeptides is replaced by a dextrorotatory amino acid with a side chain that can be coupled to a carrier compound wherein said contiguous LHRH decapeptide sequences are joined with a terminus linkage. 
     
     
       2. A peptide according to  claim 1  characterised in that it comprises an amino acid sequence that comprises the structure (SEQ ID NO: 4 ):
                     1     6        16    21         #EHWSY*LRPGQHWSY*LRPGC                
 
       wherein the amino acid * at position 6 or 16 is a dextrorotatory amino acid with a side chain that can be coupled to a carrier compound and the other amino acid * is either glycine or a dextrorotatory amino acid with a side chain that can be coupled to a carrier compound. 
     
     
       3. Peptides according to  claim 1  that A peptide that comprises at least two contiguous LHRH decapaptide sequences wherein the amino acid glycine at position  6  of at least one of the constituting LHRH decapaptides is replaced by a dextrorotatory amino acid with a side chain that can be coupled to a carrier compound wherein said decapaptides are joined with an N-terminus to N-terminus linkage, or C-terminus to C-terminus linkage and are dimerised or multimerised. 
     
     
       4. A peptide according to  claim 3  and comprising the structure:
                         1     6         16     21             #EHWSY*LRPGQHWSY*LRPGC   (SEQ ID NO:4)                              |         #EHWSY*LRPGQHWSY*LRPGC   (SEQ ID NO:4)         22   27        37    42                   
 
       wherein the amino acid * at position 6 or 16 or 27 or 37 is D-lysine or D-glutamine or another dextrorotatory amino acid with a side chain that can be coupled to a carrier compound and the other amino acid * is either glycine or D-lysine or D-glutamine or another dextrorotatory amino acid with a side chain that an be coupled to a carrier compound. 
     
     
       5. A peptide according to  claim 3  and having the structure (SEQ ID NO: 7  where residue  22  is Cys):
                      11  6 7      16 1721 22         #CQHWSY*LRPGQHWSY*LRPGC          |         #CQHWSY*LRPGQHWSY*LRPGC         23222729    37394244                   
 
       wherein the amino acid * at position  6  or  16  or  27  or  37   7  or  17  or  29  or  39  is D-lysine a D-glutamine or another dextrorotatory amino acid with a side chain that can be coupled to a carrier compound and the other amino acid * is either glycine or D-lysine a D-glutamine or another dextrorotatory amino acid with a side chain that as be coupled to a carrier compound. 
     
     
       6. A composition in which a peptide in accordance with  claim 1  is coupled to a carrier compound. 
     
     
       7. A composition in accordance with  claim 6  wherein the carrier compound is a protein. 
     
     
       8. A composition in accordance with  claim 7  wherein the carrier compound is KLH a ovalbumin. 
     
     
       9. A composition peptide in accordance with claims claim  1  additionally comprising combined with a mild adjuvant. 
     
     
       10. A composition in accordance with  claim 9  wherein the mild adjuvant is an oil phase of a water-in-oil emulsion or a double oil emulsion. 
     
     
       11. A vaccine comprising a composition peptide in accordance to  claim 1 . 
     
     
       12. A method for comprising inoculating an animal with a vaccine according to  claim 11 . 
     
     
       13. A method for comprising inoculating an animal with a vaccine according to  claim 11  wherein the an effective amount is less than about  1  mg. 
     
     
       14. A method to effect affect one or more reproductive or behavioural characteristics of an animal, characterized in that said animal is vaccinated in accordance with  claim 12 . 
     
     
       15. A method to immunocastrate a pig, characterized in that said pig is vaccinated in accordance with  claim 12 .