Specific antibodies elicited by antigen covalently linked to a synthetic adjuvant

Abstract

S-(2,3-Bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-cysteinyl-( S)-serine (Tripam-Cys-Ser), a synthetic analogue of the N-terminal part of bacterial lipoprotein, constitutes a potent B-lymphocyte activator, inducing mitosis and immunoglobulin production, and is an adjuvant of the humoral immune response. The product was covalently coupled to a nonimmunogenic oligopeptide, representing an extracytoplasmic sequence of the receptor for the epidermal growth factor (EGF-R amino acids 516-529: Asn-Leu-Leu-Glu-Gly-Glu-Pro-Arg-Glu-Phe-Val-Glu-Asn-Ser). The resulting conjugate was able to induce a specific antibody response 2 wk after a single i.p. administration in mice, as measured by ELISA assays. Controls performed by injecting either adjuvant or oligopeptide alone, or a mixture of both compounds, elicited only a marginal stimulation of the specific antibody response. The conjugate was also immunogenic in vitro. Synthetically derived lipopeptides, thus, constitute powerful agents for turning substances of low immunogenicity into potent immunogens, after conjugating them covalently to the adjuvants. This technique should have a wide application in the preparation of conventional and monoclonal antibodies, as well as for the design of synthetic vaccines.