Induction of highly specific antibodies to a hapten but not to a carrier peptide by immunization
In this application is described a composition and method for inducing in a subject anti-hapten antibodies without inducing antibodies to the carrier protein. Kits for designing and making compositions with desired haptens are also described.
1. A hapten with a chemical formula chosen from the following:
(i) N-((4R,4aR,7R,7aR,12bS)-9-hydroxy-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-3-mercaptopropanamide;
(ii) (4R,4aR,7S,7aR,12bS)-9-(3-mercaptopropanamido)-3-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl acetate;
(iii) N,N′-((4R,4aR,7S,7aR,12bS)-3-(4-(3-mercaptopropanamido)butyl)-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diyl)diacetamide;
(iv) N-((4R,4aR,7S,7aR,12bS)-7-acetamido-3-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl)-3-mercaptopropanamide;
(v) 3-mercapto-N-((4R,4aR,7R,7aS,12bS)-3-methyl-7-(2-oxopropyl)-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl)propanamide; and
(vi) N-(4-((4R,4aR,7R,7aS,12bS)-7,9-bis(2-oxopropyl)-4,4a,5,6,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3(2H)-yl)butyl)-3-mercaptopropanamide.
2. An immunoconjugate wherein a hapten of claim 1 is covalently linked to a carrier moeity.
3. An immunoconjugate comprising a hapten with a structural formula:
N-((4R,4aS,7R,7aR,12bS)-4a,9-dihydroxy-3-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-3-mercaptopropanamide.
4. The immunoconjugate of claim 2 wherein the carrier moeity is any of MPER, tetanus toxin, KLH, and CRM.
5. The immunoconjugate of claim 4 wherein the MPER is a 23 amino acid peptide identified as SEQ ID NO:1.
6. The immunoconjugate of claim 5 wherein a 15 amino acid universal T cell epitope is used as a spacer, said epitope having a sequence identified as any of SEQ ID NO:2 and SEQ ID NO:3.
7. A composition comprising an immunologically effective amount of the immunoconjugate of claim 2 and a physiologically acceptable vehicle.
8. The composition of claim 7 further comprising an adjuvant.
9. The composition of claim 8 wherein the adjuvant is L(MPLA).
10. The composition of claim 9 wherein the immunoconjugate is embedded, associated or attached to L(MPLA).
11. A method for inducing an anti-heroin immune response in a subject comprising immunizing the subject with an immunologically effective amount of the composition of claim 7 .
12. The method of claim 11 wherein the carrier is MPER or tetanus toxin.
13. A method for inducing an anti-heroin immune response without inducing an immune response to a carrier moiety in a subject comprising immunizing the subject with an immunologically effective amount of the composition of claim 10 .
14. An antibody that binds the immunoconjugate of claim 2 .
15. The antibody of claim 14 , wherein the antibody binds heroin.
16. A composition comprising the antibody of claim 14 and a physiologically acceptable vehicle.
17. A vaccine composition comprising the immunoconjugate of claim 2 .
18. The vaccine composition of claim 17 further comprising an adjuvant.
19. The vaccine composition of claim 18 wherein the adjuvant is L(MPLA).
20. The immunoconjugate of claim 3 wherein the hapten is covalently linked to a carrier moiety, wherein the carrier moeity is any of MPER, tetanus toxin, KLH, and CRM.
21. The immunoconjugate of claim 20 wherein the MPER is a 23 amino acid peptide identified as SEQ ID NO:1.
22. The immunoconjugate of claim 21 wherein a 15 amino acid universal T cell epitope is used as a spacer, said epitope having a sequence identified as any of SEQ ID NO:2 and SEQ ID NO:3.
23. A composition comprising an immunologically effective amount of the immunoconjugate of claim 3 and a physiologically acceptable vehicle.
24. The composition of claim 23 further comprising an adjuvant.
25. The composition of claim 24 wherein the adjuvant is L(MPLA).
26. The composition of claim 25 wherein the immunoconjugate is embedded, associated or attached to L(MPLA).
27. A method for inducing an anti-heroin immune response in a subject comprising immunizing the subject with an immunologically effective amount of the immunoconjugate composition of claim 23 .
28. The method of claim 27 wherein the immunoconjugate composition further comprises a carrier, wherein said carrier is MPER or tetanus toxin.
29. A method for inducing an anti-heroin immune response without inducing an immune response to a carrier moiety in a subject comprising immunizing the subject with an immunologically effective amount of the composition of claim 26 .
30. An antibody that binds the immunoconjugate of claim 3 .
31. The antibody of claim 30 , wherein the antibody binds heroin.
32. A composition comprising the antibody of claim 30 and a physiologically acceptable vehicle.
33. A vaccine composition comprising the immunoconjugate of claim 3 .
34. The vaccine composition of claim 33 further comprising an adjuvant.
35. The vaccine composition of claim 34 wherein the adjuvant is L(MPLA).