Comparison of conventional adjuvants and 'adjuvant-free' monoclonal antibody targeting for stimulating antibody responses against a conjugate of luteinizing hormone releasing hormone and avidin.
A conjugate of luteinizing hormone releasing hormone (LHRH) and avidin was used for immunizing mice and sheep. In mice, a range of adjuvants co-administered with the conjugate was shown to affect antibody titre and isotype. The commercially available Montanide and Ribi adjuvant emulsions, polyadenylic-polyuridylic acid, Quil A and Freund's complete adjuvant all produced high antibody titres to LHRH (reciprocal titre range 8000-20,000) and avidin (range 9000-35,000). Alhydrogel, Pluronic gel, Immunostim, DEAE-Dextran and muramyl dipeptide were weak to moderately effective (reciprocal titre ranges of 1300-5000 for LHRH and 3000-6000 for avidin, respectively). With Quil A, the response to avidin in mice was found to consist of roughly equal proportions of the IgG1, IgG2a and IgG2b isotypes. In contrast, the response to avidin using the other adjuvants and to LHRH consisted predominantly of the IgG1 isotype. An 'adjuvant-free' immunization strategy was attempted by targeting the LHRH-avidin conjugate to class II major histocompatibility complex (MHC) determinants on cells of the immune system. Using an immunoconjugate formed by linking LHRH-avidin to an antibody specific for mouse and sheep class II molecules, a twofold augmentation of titres relative to controls was obtained in mice. These antibodies were almost exclusively of the IgG1 isotype. In contrast, monoclonal antibody targeting in sheep resulted in a significantly enhanced immune response (reciprocal titres of 15,000 and 20,000 for LHRH and avidin, respectively) which was comparable to that achieved by immunizing with Quil A as adjuvant. Both the monoclonal antibody targeting and Quil A treatments tended to favour the production of antibody isotype IgG1 over IgG2.(ABSTRACT TRUNCATED AT 250 WORDS)
Tiong
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Bunge Pty Ltd, Scientific and Technical Services Division, North Melbourne, Victoria, Australia.
Gill
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Lofthouse
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Puri
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000917:Antibody Formation; D001360:Avidin / Q000008:administration & dosage / Q000276:immunology*; D003269:Contraception, Immunologic / Q000379:methods; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012756:Sheep
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D001360:Avidin; D007987:Gonadotropin-Releasing Hormone