DRUG-SPECIFIC ANTIBODIES - T-CELL EPITOPE-LIPOPEPTIDE CONJUGATES ARE POTENT ADJUVANTS FOR SMALL ANTIGENS IN-VIVO AND IN-VITRO

To generate conventional or monoclonal antibodies for the serological detection of drugs, antibiotics, toxins and other low molecular mass s ubstances, a suitable and effective adjuvant is needed. Lipopeptides d erived from a major component of the bacterial cell wall constitute po tent nontoxic and nonpyrogenic immunoadjuvants when mixed with convent ional antigens. Here we demonstrate that the synthetic lipopeptide (pa lmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-serine (P3CS) coupled to a T- h-cell epitope (P3CS-T-b) can efficiently enhance the specific immune response against low molecular weight compounds in different species. In the presence of the synthetic lipopeptide P3CS-T-b, the peptides wh ich are per se nonimmunogenic stimulated a specific humoral immune res ponse in mice after intraperitoneal application. Mixtures containing a djuvants without the Th sequence showed no significant antibody induct ion. A marked enhancement of the humoral immune response was obtained with the low molecular mass antigens Iturin A(L), Herbicolin A and Mic rocystin (MLR) coupled to poly-1-lysin (MLR-PLL), in rabbits and in ch ickens. Lipopeptide-T-b cell epitope conjugates also constituted adjuv ants for the in vitro immunization of either human mononuclear cells o r mouse B-cells with MLR-PLL; after fusion of the immunized cultures w ith the heteromyeloma cell lines CB-F7 or the mouse myeloma cell line SP 2/0, respectively, we observed a significantly increased yield of a ntibody secreting hybridomas. (C) 1997 International Society for Immun opharmacology.