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用于抗促性腺激素释放激素疫苗的合适载体分子的研究。

Investigation into suitable carrier molecules for use in an anti-gonadotrophin releasing hormone vaccine.

作者信息

Ferro V A, Stimson W H

机构信息

University of Strathclyde, Department of Immunology, Glasgow, Scotland.

出版信息

Vaccine. 1998 Jul;16(11-12):1095-102. doi: 10.1016/s0264-410x(98)80104-7.

Abstract

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.

摘要

性腺功能可通过对促性腺激素释放激素(GnRH)进行免疫中和来控制,使用与载体分子及合适佐剂相连的类似物GnRH-半胱氨酸。在本研究中,对四种不同类型的载体分子进行了研究:(a)单链和支链氨基酸聚合物——[聚(D-谷氨酸,D-赖氨酸)和聚(苯丙氨酸,谷氨酸)-聚(DL-丙氨酸)-聚(赖氨酸)];(b)细菌类毒素——白喉毒素(DT)和破伤风毒素(TT);(c)合成的辅助性T细胞表位——源自疟原虫环子孢子蛋白(CS)和麻疹病毒融合蛋白(MVF);以及(d)甲状腺球蛋白(Thy)——一种大分子蛋白质。还研究了非离子表面活性剂囊泡(NISV)和氢氧化铝基佐剂(明矾)的作用。尽管吸附在明矾上的GnRH-半胱氨酸-DT、GnRH-半胱氨酸-TT和GnRH-半胱氨酸-Thy以及掺入NISV中的二聚化合成辅助性T细胞表位构建体都产生了良好的抗体反应,但要导致性腺形态变化并完全抑制精子发生,需要达到临界抗体滴度。只有破伤风类毒素和二聚化辅助性T细胞表位才能实现这一点。

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