VIP技术:对抗疾病的新利器,无需疫苗直接产生抗体
生物通 · 2014/09/21
数十年来,人们一直在努力开发广谱有效的疫苗,希望阻断HIV、疟疾、肺结核等疾病的传播。疫苗将抗原引入机体,诱发相应的免疫应答,生成相应的抗体。那么,能不能直接给机体下达指令,让它生成针对某种疾病的特异性抗体呢?诺贝尔奖得主,加州理工学院的David Baltimore教授开发了这样的技术——VIP。


David Baltimore(左)

数十年来,人们一直在努力开发广谱有效的疫苗,希望阻断HIV、疟疾、肺结核等疾病的传播。尽管他们取得了一定的进展,但这类疫苗现在依然还没面世。如果疫苗就是起不了作用,那该怎么办呢?诺贝尔奖得主,加州理工的David Baltimore教授找到了另一条途径。

疫苗将抗原引入机体,诱发相应的免疫应答,生成抵御感染的抗体和T细胞。能不能直接给机体下达指令,让它生成针对某种疾病的特异性抗体呢?Baltimore团队就开发了这样的技术,并将其命名为VIP(vectored immunoprophylaxis)。最初他们用这个方法来免疫HIV,结果大获成功。现在,VIP已经被用来对抗其他感染性疾病,比如流感、疟疾和丙肝。

“这个技术可以广泛用于人类面临的多种疑难病,尤其是在不发达地区,”Baltimore说。VIP需要先鉴定到能够抑制感染的抗体,然后将其编码基因整合到腺相关病毒AAV载体中。AAV是一种无害的病毒,在基因疗法的临床试验中有上佳的表现。AAV注射到肌肉组织之后,它携带的基因就会指导肌肉组织生成特异性抗体,这些抗体能够进入血液循环,帮助机体抵抗感染。

2011年,Baltimore研究团队在《Nature》上发表了这一技术。他们通过VIP对小鼠进行了有效保护,使它们免受HIV的感染。Alejandro Balazs是当时这篇文章的第一作者。研究显示,只需注射一次小鼠就能够产生高水平的抗体,连续几个月有效对抗大剂量的HIV感染。现在Baltimore的研究团队正在和制药公司合作,为人类临床试验做准备。

后来,Baltimore实验室又开发了针对A型流感的VIP技术。虽然现在的流感疫苗能够抵御病毒感染,但流感病毒总能演化出抗性,A型流感尤其令人头痛。为此流感疫苗每年都要翻新,而且有时还会失效。

大约五年前,人们鉴定了一类能够阻断多种流感病毒的抗体,这种抗体能结合比较保守的病毒茎部。2013年,Baltimore团队将两个编码这种抗体的基因整合到AAV中。研究显示,注射了载体的小鼠能够抵御多种流感病毒,包括H1、H2和H5。这种VIP处理对于免疫功能较弱的小鼠也同样有效。这一成果当时发表在《Nature Biotechnology》杂志上。

后来其他团队也开始用Baltimore开发的VIP技术,对抗疟疾、丙肝和肺结核。

今年八月,Johns Hopkins大学的研究团队与Baltimore合作在美国国家科学院院刊PNAS上发表了VIP的新成果。在这项研究中,注射了VIP的小鼠有70%能够抵御疟原虫的感染。那些生成抗体特别多的小鼠,全都受到了有效的保护。

“这还只是第一代抗体,”Baltimore说,“现在人们可以尝试开发更厉害的抗体。”

9月17日,Rockefeller大学研究团队与Baltimore合作的研究登上了《Science Translational Medicine》的封面。研究显示,VIP递送的三个丙肝抗体,能够有效保护小鼠不受感染。研究人员还发现,在已经受到感染的小鼠体内,VIP处理能够暂时清除病毒。下一步他们会想办法防止疾病的复发。

此外,还有一项研究正在评估VIP预防肺结核的能力。由于能中和结核杆菌的抗体不多,这项研究特别有挑战性。

Baltimore表示,这么多团队用VIP技术对抗疾病,令人感到非常振奋。

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