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开发一种使用促性腺激素释放激素-半胱氨酸-结核菌纯蛋白衍生物的激素中和疫苗,用于治疗雌激素依赖性疾病。

Development of a hormone neutralizing vaccine, using GnRH-glycys-PPD, for use in the treatment of oestrogen-dependent disorders.

作者信息

Ferro V A, O'Grady J E, Notman J, Stimson W H

机构信息

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

出版信息

Ther Immunol. 1995 Jun;2(3):147-57.

PMID:8885133
Abstract

The aim of this study was to develop an effective and nontoxic vaccine, suitable for use in humans, which was capable of effectively controlling oestrogen levels. Female Sprague-Dawley rats were immunized with a conjugated analogue of gonadotrophin releasing hormone, GnRH-glycys-PPD. This resulted in high levels of neutralizing antibody which disrupted GnRH function and consequently caused a reduction in serum oestrogen. The effect of oestrogen deprivation correlated well with ovarian failure and gonadal atrophy. An examination was made of various adjuvants in conjunction with the analogue to determine the suitability of the combinations in the formulation of an effective human vaccine. This investigation included a novel adjuvant, non-ionic surfactant vesicles (NISV); the results showed that NISV are completely nontoxic and in terms of potentiating and sustaining an immune response, compare favourably with Freund's adjuvant and alum. In addition the long term effects of immunization were investigated and the data showed that immunoneutralization of GnRH effectively suppresses fertility on a long-term basis.

摘要

本研究的目的是开发一种有效且无毒的、适用于人类的疫苗,该疫苗能够有效控制雌激素水平。用促性腺激素释放激素的共轭类似物GnRH-半胱氨酸-PPD对雌性斯普拉格-道利大鼠进行免疫。这导致了高水平的中和抗体,该抗体破坏了GnRH功能,从而使血清雌激素水平降低。雌激素缺乏的影响与卵巢功能衰竭和性腺萎缩密切相关。研究了各种佐剂与该类似物的组合,以确定这些组合在制备有效的人用疫苗方面的适用性。这项研究包括一种新型佐剂,即非离子表面活性剂囊泡(NISV);结果表明,NISV完全无毒,在增强和维持免疫反应方面,与弗氏佐剂和明矾相比具有优势。此外,还研究了免疫的长期影响,数据表明,GnRH的免疫中和作用能长期有效抑制生育能力。

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