Induction of highly specific antibodies to a hapten but not to a carrier peptide by immunization

摘要

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. In this application Is disclosed a synthetic liposome composition comprising liposomes (L) containing monophosphoryl lipid A (MPLA) [L(MPLA)] and an immunoconjugate comprising a carrier and a hapten. In one embodiment, the carrier is a 23 amino acid hydrophobic membrane proximal external region peptide (MPER) derived from the gp41 transmembrane protein of HIV-1 that spontaneously associates with the outer surface of bilayers of liposomes containing MPLA during liposome formation.

主权项

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.