Investigation into suitable carrier molecules for use in an anti-gonadotrophin releasing hormone vaccine.
Gonadal function can be controlled through immunoneutralisation of gonadotrophin releasing hormone (GnRH), with an analogue, GnRH-glycys, linked to a carrier molecule and an appropriate adjuvant. In this study, four different types of carrier molecule were investigated: (a) single and branched amino acid polymers--[poly-(D-glu, D-lys) and poly-(phe, glu)-poly(DL-ala)-poly(lys)]; (b) bacterial toxoids--diphtheria (DT) and tetanus (TT); (c) synthetic T-helper epitopes--derived from malarial circumsporozite protein (CS) and measles virus fusion protein (MVF); and (d) thyroglobulin (Thy)--a large protein. The effect of non-ionic surfactant vesicles (NISV) and an aluminum hydroxide based adjuvant (alum), was also examined. Although good antibody responses were achieved with GnRH-glycys-DT, GnRH-glycys-TT and GnRH-glycys-Thy, adsorbed onto alum and the dimerised synthetic T-helper epitope constructs, incorporated into NISV, a critical antibody titre was necessary to result in morphological changes in the gonads and complete suppression of spermatogenesis. This was only achieved with tetanus toxoid and the dimerised T-helper epitopes.
University of Strathclyde, Department of Immunology, Glasgow, Scotland.
V A
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Ferro
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Stimson
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D004168:Diphtheria Toxoid / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014612:Vaccines
D000276:Adjuvants, Immunologic; D000596:Amino Acids; D002352:Carrier Proteins; D004168:Diphtheria Toxoid; D000939:Epitopes; D011108:Polymers; D013745:Tetanus Toxoid; D014612:Vaccines; D007987:Gonadotropin-Releasing Hormone