Factors influencing the immunogenicity of the haptenic drug chlorhexidine in mice--Part I. Molecular requirements for the induction of IgE and IgG anti-hapten antibodies.
The immunogenicity of a novel hapten, the anti-microbial agent, chlorhexidine (1,1'-hexamethylene bis [5-(p-chlorophenyl)biguanide]) was assessed in mice, using alum as adjuvant. The i.p. injection of electrostatically-linked chlorhexidine + keyhole limpet haemocyanin (KLH) mixtures induced low level primary IgG anti-chlorhexidine antibody synthesis. In contrast, covalently-linked chlorhexidine-KLH complexes induced both IgE and IgG anti-chlorhexidine antibody synthesis. Covalent binding was facilitated by the N-chlorination of secondary amide groups on the biguanide moeities of the chlorhexidine molecule. The immunogenicity of such complexes was related to the degree of conjugation of chlorhexidine to KLH; which, in turn, was related to the molarity of chlorine used to effect N-chlorination. Immune responses to covalently-linked complexes could be enhanced by carrier priming. The induction of low levels of IgG anti-hapten antibodies by electrostatically-linked complexes may reflect T cell-independent specific B cell activation, either by chlorhexidine itself or by a "pseudo-plurivalent" chlorhexidine + KLH antigen.
D000818:Animals; D002710:Chlorhexidine / Q000276:immunology*; D002713:Chlorine / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C
D006241:Haptens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D002713:Chlorine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D002710:Chlorhexidine