A synthetic analogue of Escherichia coli lipoprotein, tripalmitoyl pentapeptide, constitutes a potent immune adjuvant.
Lipoprotein from the outer membrane of Escherichia coli and other Enterobacteriaceae constitutes a potent B lymphocyte mitogen and polyclonal activator in various species. Tripalmitoyl pentapeptide (S-(2,3-bis-(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-cysteinyl -(S)-seryl-(S)-seryl-(S)-asparaginyl-(S)-alanine) is a synthetic analogue of the N-terminal part of lipoprotein and has, in all assays tested, a biologic activity similar to native lipoprotein. It also exhibits a strong adjuvant activity in vitro: In the presence of 3.3 to 33.3 micrograms/ml of tripalmitoyl pentapeptide, the stimulation of the primary antibody response toward underivatized sheep red blood cells (SRBC) and toward trinitrophenylated (TNP-) SRBC was markedly enhanced, as measured by a direct hemolytic plaque assay. At optimal mitogen- and antigen-doses, plaque formation was increased up to 100-fold, and at suboptimal doses (0.03 to 0.3 microgram/ml) a 10- to 60-fold increase of plaque numbers was achieved. In the presence of tripalmitoyl pentapeptide, the antigen-specific IgM response was increased about sevenfold and the IgG response was augmented about 10-fold, as measured by ELISA. Similarly, in the secondary in vitro response to TNP-SRBC, a 7 to 10-fold enhancement of the antibody titer was obtained in the presence of the adjuvant. The application of tripalmitoyl pentapeptide and antigen had to occur concurrently in order to achieve a strong adjuvant effect. Addition of tripalmitoyl pentapeptide to the cell cultures 1 day after or 1 day before antigen application had no significant positive effect, and in several instances a decrease in antibody production was found. Thus, tripalmitoyl pentapeptide, a well-characterized synthetic product available in major amounts, constitutes a potent immune adjuvant for potential animal and clinical use.
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology; D006462:Hemolytic Plaque Technique; D007136:Immunoglobulins / Q000032:analysis; D055666:Lipopeptides; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D055666:Lipopeptides; D009842:Oligopeptides; C038293:2,3-bis(palmitoyloxy)-2-propyl-N-palmitoyl-cysteinyl-seryl-seryl-asparaginyl-alanine