Effects of adjuvant, dose and carrier pre-sensitisation on the immunisation efficacy of a GnRH analogue.

Drug design and discovery Pub Date : 1996-12-01
V A Ferro, W H Stimson
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Abstract

A GnRH-neutralising vaccine, with potential applications in the treatment of human sex hormone-dependent disorders, was developed by conjugating GnRH-glycys to tetanus toxoid. An evaluation of adjuvant, dose and carrier pre-sensitisation was made. Male rats immunised with the conjugate, adsorbed onto alum, showed higher anti-GnRH antibody levels and suppressed testosterone concentrations, compared with animals immunised without adjuvant. Conjugate administration in a four injection regime proved to be the most effective in disrupting fertility, as assessed by the degree of lowered testosterone levels and gonadal atrophy. Pre-sensitisation with tetanus toxoid had an initial marked effect on immunisation, observed following 2 drug doses; the pre-sensitised animals showed a lower antibody response to the conjugate than did the non-primed animals. However, as the number of drug doses increased to 4, there was no significant difference between the primed and non-primed animals.

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佐剂、剂量和载体预致敏对GnRH类似物免疫效果的影响。
通过将gnrh -甘氨酸与破伤风类毒素结合,开发了一种gnrh -中和疫苗,可能应用于治疗人类性激素依赖性疾病。对佐剂、剂量和载体的预致敏性进行了评价。与未接种佐剂的雄性大鼠相比,接种了这种结合物并吸附在明矾上的雄性大鼠显示出更高的抗gnrh抗体水平和抑制睾丸激素浓度。通过降低睾丸激素水平和性腺萎缩的程度来评估,四次注射的结合给药被证明在破坏生育方面是最有效的。破伤风类毒素预致敏对免疫有最初的显著效果,观察2次药物剂量;预致敏动物对偶联物的抗体反应低于未致敏动物。然而,当药物剂量增加到4次时,启动和未启动的动物之间没有显著差异。
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