Immunological castration by a totally synthetic vaccine: modification of biological properties of LH-RH after conjugation to adjuvant-active muramyl peptide.
Recently, we demonstrated that immunological castration of male mice can be obtained by immunization with Luteinizing Hormone-Releasing Hormone (LH-RH) directly coupled to NAcMur-L-Ala-D-isoGln-L-Lys (MDP-Lys) without carrier and Freund's Complete Adjuvant (FCA) but in the presence of Polyvinyl-Pyrrolidone (PVP). In the present report, we have observed that: (a) immunization by the conjugate, LH-RH-MDP-Lys, was very effective even in absence of PVP, and this conjugate was more active than other conjugates containing MDP coupled to LH-RH fragments; (b) a strong secondary response could be observed by the administration of free LH-RH suggesting that the endogenous secretion of LH-RH might elicit a boosting effect; (c) administration of MDP-Lys coupled to LH-RH decreased the pyrogenicity of the glycopeptide; (d) such a conjugation also decreased the hormonal activity of the antigen although it enhanced its immunogenicity. These results show that a conjugate (2000 dalton) of a decapeptide hormone with a synthetic adjuvant glycopeptide can induce immunological castration in mice after administration in saline. The immunopharmacological properties of the conjugate and its conditions of efficacy suggest that such an approach could find clinical application.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D000937:Antigen-Antibody Reactions; D002369:Castration; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000276:immunology*; D007114:Immunization; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D013737:Testis / Q000473:pathology
D000276:Adjuvants, Immunologic; D007987:Gonadotropin-Releasing Hormone; D000119:Acetylmuramyl-Alanyl-Isoglutamine