国产避孕疫苗研究现状和前景

CURRENT STATUS AND PROSPECT OF CHINA'S CONTRACEPTIVE VACCINE RESEARCH

国产第 1代避孕疫苗已经研制成功。疫苗构建是采用妊娠特异性强、妊娠期短暂出现的糖蛋白激素———人类绒毛膜促性腺激素 (humanchorionicgonadotropichormone,hCG)为靶抗原 ,应用蛋白质工程技术研制的。抗原不但保留了hCG的生物活性 ,而且不与垂体的其他 3种激素交叉 ,并克服了“自身免疫耐受性” ,使免疫系统对它作为“非自身”而产生抗体反应。以此构建的第 1代避孕疫苗原型 ,经临床前非人灵长类的免疫原性、安全性和毒理学试验达到预期效果后 ,参照世界卫生组织人类生殖特别规划委员会避孕疫苗任务组指导委员会制订的第 1期临床试验方案 ,两位主要研究工作者和 10位输卵管结扎妇女志愿者接受了免疫注射 ,在严密的监护下完成了国产第 1代避孕疫苗的第 1期临床预初试验 ,结果证明疫苗在人体可诱发抗体反应 ,免疫反应有可逆性和记忆。受试者无任何毒副反应 ,月经周期正常 ,排卵不受影响。第 2代新型避孕疫苗的研究 ,将在第 1代原型的基础上 ,通过基因和蛋白质工程技术 ,解决抗原的大量生产、挖掘内在的决定簇 ,或引入外源性生殖活性抗原 ,构建多特异性多功能复合免疫原 ,发展复合避孕疫苗 ,这些都将是十分有吸引力的研究领域。

China's first generation of contraceptive vaccine has been developed through the multi center collaboration research program supported by National Research Project during the past ten years.The basic principle of the vaccine's formulation was designed to use a key pregnant depentent,transit present,tissue specific and molecular structure well known glycoprotein hormone—human chorionic gonadotropic hormone through the application of protein engineering techniques,the crossreactivity with three other pituitary glycoprotein hormones and the immunotolerance of the body to this “self” hormone have been overcome and the biological activity of hCG remained intact.Pre clinical non human primate toxicology & safety study has been carried out in Guangdong Primate Center successfully.Two principal investigators of this research project have received the pilot inoculation of China's first generation of contraceptive vaccine to obtain the direct experience of immune response,ten volunteers of tubular ligated female have entered into the first phase clinical pilot trial in 1995 and successfully proved that China's first generation of hCG controceptive vaccine is immunogenic,safe,no toxic reactions in human beings. The formulation of second generation of a new vaccine to enhance the immunogenecity through protein and genetic engineering is now in progress.