Lipopeptides: adjuvanticity in conventional and genetic immunization.
Synthetic lipopeptides derived from the bacterial cell wall component lipoprotein activate B-lymphocytes and macrophages/monocytes in vitro. In vivo they constitute potent immunoadjuvants for a broad range of different antigens and species comparable or superior to Freund's adjuvant. Here, we demonstrate that P(3)CSK(4), representing a highly active lipopentapeptide derivative in vitro, significantly enhances and accelerates the humoral immune response to tetanus toxoid. P(3)CSK(4) could substitute for up to 90% of the antigen without any decrease in the specific IgG level, and the presence of the lipopeptide resulted in a prolonged production of specific IgG in time. Investigations using P(3)CSK(4) as an adjuvant in genetic immunization confirmed earlier data demonstrating that lipopeptides constitute adjuvants for low-immunogenic DNA constructs and/or for application routes resulting in weak immune responses. We monitored a lipopeptide-dependent shift from a Th1-type to Th2-type response, when DNA immunization was followed by i.p. administration of the lipopeptide adjuvant.
Mittenbühler
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Institut für Molekulare Medizin und Zellforschung, Universitätsklinikum Freiburg, AK Tumorimmunologie/Vakzine, Stefan-Meier-Str. 8, D-79104 Freiburg, Germany. mittenb@uni-freiburg.de
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Heinevetter
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Bessler
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Huber
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D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D019470:Biolistics; D005260:Female; D007114:Immunization; D008074:Lipoproteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D008074:Lipoproteins; D013745:Tetanus Toxoid; D019444:Vaccines, DNA; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine