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历经三十年的研发 艾滋病疫苗离上市还有多远?
2017-09-15 13:16:51 中国青年网
中国疾病预防与控制中心的研究人员也开发了具有自主知识产权的艾滋病疫苗,他们利用天坛痘苗病毒作为载体,表达HIV表面糖蛋白抗原作为疫苗,临床I期试验显示了该疫苗安全性,临床II期试验也已完成,临床结果有待公布。
知己知彼
艾滋病疫苗的研发之所以如此艰难,主要有几个重要原因。一是艾滋病病毒非常善变,仅其包膜糖蛋白的可能突变形式就达13000种以上,单个或少数几种疫苗很难对付变化莫测的艾滋病病毒;二是艾滋病病毒善于潜伏,一般潜伏期为8-10年,病毒感染人体免疫细胞后,会将病毒DNA整合到宿主基因组中,很难清除;三是艾滋病病毒只对人类造成伤害,灵长类动物虽然也有类似的病毒SIV,但是却不发病,很多HIV疫苗在猕猴身上能产生对抗SIV的中和抗体,但是在人体临床试验中却不能诱导产生中和HIV的特异抗体。
这些都是艾滋病病毒自身特点,艾滋病病毒是现已发现病毒中结构最为复杂的,经过三十多年的努力,科学家们对其分子结构、作用机制、起源历史等可以说是了如指掌。但是,研发艾滋病疫苗最主要的困难还在于,人们对机体如何应对艾滋病病毒的免疫机制还不是很清楚,这也是最近科学家们努力的主要方向。
天花、埃博拉等病毒感染人体后,感染者中都会有一定比例自愈者,但是尚没有发现一例艾滋病自愈病例,而且艾滋病感染者对艾滋病病毒的免疫反应较弱,刚开始只是产生一些非特异抗体,要等到感染数年之后,才能生产特异的中和抗体,但是此时病毒往往已经遍布全身,在众多的免疫细胞中大量繁殖,甚至会找到一些抗体难以抵达的藏身之所躲藏起来,导致这些中和抗体很难彻底清除病毒。
不过,最近有人在艾滋病感染者体内发现少量能中和大多数艾滋病病毒亚型的广谱中和抗体,引起艾滋病研究领域科学家的广泛关注,大家希望能设计出特效疫苗,激发机体大量产生这种广谱中和抗体。2016年9月,一个瑞士苏黎世大学科学家领导的科研团队在《自然医学》杂志报道称,通过对近4500名艾滋病感染者进行深入分析,发现其中有239名体内产生了广谱中和抗体,而这些广谱中和抗体含量与病毒载量、密度以及感染时间相关,另外该研究还发现黑人感染者产生的中和抗体量要显著高于白人,而且不同的病毒亚型也对中和抗体的产生有一定影响。尽管目前所有艾滋病疫苗均没能引发机体产生广谱中和抗体,包括RV144免疫方案和HVTN-505免疫方案,但是这项研究对艾滋病疫苗研发和免疫方案设计有所帮助。
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