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人类抗艾研究重大进展 湖北两海外学子贡献突出
http://www.jznews.com.cn 发布时间：2010-08-13 10:22
新闻提要：今日出版的最新一期全球顶级学术期刊《科学》(Science)，将发表两份由美国国立卫生研究院(NIH)科学家撰写的研究报告，宣布他们从艾滋病病毒感染者的血样中，成功分离出两个自然产生的、能够中和约90%已知艾滋病毒毒株的单克隆抗体。这是迄今为止全球分离出的最强效广谱抗艾抗体。
荆楚网消息 今日出版的最新一期全球顶级学术期刊《科学》(Science)，将发表两份由美国国立卫生研究院(NIH)科学家撰写的研究报告，宣布他们从艾滋病病毒感染者的血样中，成功分离出两个自然产生的、能够中和约90%已知艾滋病毒毒株的单克隆抗体。这是迄今为止全球分离出的最强效广谱抗艾抗体。
此前，《科学》杂志网络版已于7月8日先行发表了这两份报告。令人欣喜的是，这两份研究报告的第一作者，都是湖北高校毕业后赴美深造的中国科学家。其中，宣布发现该广谱强效单克隆抗体研究报告的第一作者伍雪玲，1994年毕业于原同济医科大学(现华中科技大学同济医学院)，后赴美获博士学位，一直从事艾滋病病毒与抗体研究，2006年进入NIH工作；另外一篇研究报告对该抗体与艾滋病病毒结合的结构进行了分析，第一作者周同庆，1989年毕业于武汉大学，在中科院获博士学位后赴美，2001年进入NIH工作。
人类在上世纪80年代初发现艾滋病以来，全球有约6000万人感染了艾滋病病毒，2500万人死于相关疾病，但艾滋病的预防和治疗一直没有取得突破性进展。其中一个关键环节是，由于对广谱抗艾抗体的研究不足，抗艾疫苗的开发也就无从有效进行。
因此，基于上述成果，NIH发布官方新闻指出，NIH的科学家已开始相关疫苗的开发，以期诱导人体免疫系统产生类似的抗体反应，从而将艾滋病病毒阻断在传染阶段。
这两份研究报告的署名作者分别有24人和18人。伍雪玲和周同庆能够分别成为两份报告的第一作者，显示出他们在研究中所起的实质作用。
近一个月来，记者通过电子邮件多次采访伍雪玲博士。她告诉记者，自2008年4月接到课题后，与同事们进行了难以数计的各种实验，直到2009年8月，终于从一名60岁非洲同性恋男子血样的2500万个血细胞中，分离出了最强抗艾抗体。
昨日，伍雪玲高兴地给记者发来电子邮件称：“我们已经用同样的方法，从另一位病人的血样中分离出了类似抗体，说明这种抗体不是一个病人所独有的
“要知道能成功，还叫什么探索呢”
――伍雪玲博士讲述最强抗艾抗体发现之路
记者是7月下旬与伍雪玲博士取得联系的。其间，她通过电子邮件，回顾了她们发现最强效广谱抗艾抗体的科研之路。下面，就是其中的摘录。
受命：“成功了皆大欢喜，失败了你也必须相信我已尽力”
2008年4月以前，整个艾滋病抗体研究领域弥漫着一种悲观情绪，那就是没有普遍意义上的广谱抗艾病毒的中和单克隆抗体存在，而这一类抗体反应正是一个有效的、能够预防艾滋病毒感染的疫苗所必需的。在这个问题面前，科学家们面临十字路口，理想中的那种单克隆抗体，究竟有没有？找还是不找啊？最终，我所在的NIH过敏与传染病研究所疫苗研究中心决定，找，一定要找！
我和同事，同样来自中国大陆的李宇星博士被指定承担寻找这种抗体的具体工作。我当时其实很为难，别人都找不出来，凭什么我就能找出来呢？但科研的探索性质就是这样：什么是探索啊？要知道能成功的还探索什么呀？所以我对中心负责人说，我只能尽心一试。成功了皆大欢喜，失败了你也必须相信我已尽力。
实验：不断承受各种失败
分离抗体的基本步骤确定后，实施起来却困难重重。几乎设计中的每一步，实施起来都有困难，特别是单细胞PCR，在经过实验条件优化后，也只能拿到25%到50%的阳性率。在体外克隆和蛋白表达的过程中也是处处陷阱，蛋白表达的成功率常常低于60%。更要命的是，在最后测定抗体抗原的结合试验之前，没办法知道分离出来的抗体特异性，而人体血中的抗体特异性以百亿计！我和李宇星经常在经过近两个月的辛苦工作后，拿着提纯出来的十几二十几个抗体去做与抗原的结合实验，结果实验盘上一片空白！那意味着过去的两个月都是“杨白劳”，一切都得从头再来！有几次我看着那些空白的实验盘，整个人难受得几乎都要吐出来。
但是，能够承受失败也是科研人员必备的素质之一。一遭受失败就崩溃的人是不可能在实验室里留下来的。
转机：创新带来成功
转机出现在2009年6月至8月间，我们决定放弃常规的以艾滋病毒表面蛋白来做抗原标记的办法，而采用中心疫苗载体实验室主任杨志勇和周同庆博士做的异化蛋白。这个异化蛋白是在艾滋病毒表面蛋白的基础上，通过计算机的模拟和优化，改变了一些蛋白表面的构相，使它不再是百分百的艾滋病毒蛋白，但艾滋病毒蛋白与其细胞受体的原始结合位点得以保留。就是从这样标记并分离的29个单个B细胞中，我成功分离了12个抗体，其中3个与异化蛋白结合的数据是对的，那3个抗体就是VRC01，VRC02和VRC03。最终的病毒中和实验表明，它们3个都是广谱的抗艾滋病毒的中和抗体，而其中VRC01和VRC02对艾滋病毒株的涵盖率达到91%，这大大超过我们的预期！
影响：比尔・盖茨是不是该吃帽子了？
经过几个月相关数据的完善和整理，我们团队的论文于2010年1月底投到《科学》杂志，并于7月8日在该杂志的网络版发表。当天NIH过敏与传染病研究所就这一成果做了专门的新闻发布。美国各大媒体做了大量报道，《华尔街日报》所披露的我们所用的病人血样来自一60岁的非洲同性恋男子，甚至连我们自己都是第一次知道。
从艾滋病毒疫苗研发的角度讲，这一成果解决了好几个难题。首先，人体能不能产生这样的抗体反应已不再是问题，因为抗体活生生地摆在那儿了。其次，抗体VRC01与抗原结合的结构也已解出并发表，任何一个实验室都可以参照这个信息去设计疫苗。最后，抗体VRC01可以立刻进行临床实验，看将它与其他特异性的中和抗体联合使用是否有治疗效果。再者，因为有了这样的成功例子，从病人血样中分离出更多的中和抗体已经不再成为难题。而也是因为这些抗体对抗艾疫苗所提供的具体指导意义，抗艾疫苗似乎不再遥不可及。比尔・盖茨也因为在2005年声称“10年内若发现艾滋病疫苗我就吃我的帽子”，而被美国媒体开问：是不是该吃帽子了？(湖北日报 记者 黄磊、周芳)
新闻来源：荆楚网 2010-08-13 10:22 编辑：任仲杰
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Significant progress in research of human anti-Ai Hubei two outstanding contributions of overseas students
http://www.jznews.com.cn Published :2010-08-13 10:22
Headlines: today published the latest issue of the world's top academic journal "Science" (Science), will deliver two by the U.S. National Institutes of Health (NIH) research report written by scientists announced that they infected with HIV from blood samples in successfully isolated two naturally occurring, can be in about 90% of the known strains of HIV monoclonal antibodies. This is by far the world's most potent broad-spectrum isolated anti-AI antibody.
Sports Network today published the latest issue of the world's top academic journal "Science" (Science), will deliver two by the U.S. National Institutes of Health (NIH) research report written by scientists announced that they infected with HIV from blood samples of successfully isolated two naturally occurring, can be in about 90% of the known strains of HIV monoclonal antibodies. This is by far the world's most potent broad-spectrum isolated anti-AI antibody.
Prior to that, "Science" magazine online edition was first published on July 8 the two reports. It is gratifying that this first of two studies are U.S. studies after graduating from college in Hubei Chinese scientists. Among them, announcing the potent broad-spectrum monoclonal antibody study's first author Wu Xueling, Tongji Medical University in 1994, graduated from the original (now Tongji Medical College), Ph.D., after the United States has been engaged in HIV and antibody, into the NIH in 2006 working; also a study of the antibody binding structure with HIV was analyzed, the first of week of Celebration, graduated from Wuhan University in 1989, after the United States at the Chinese Academy of Sciences Ph.D., 2001 into the NIH work.
Humanity in the early 80s of last century since the discovery of AIDS, about 6000 million people worldwide infected with HIV, 2500 people died related diseases, but AIDS prevention and treatment has not been a breakthrough. One of the key, because of the broad-spectrum anti-AI antibody deficiencies, the development of vaccines against AI there can be no effective.
Therefore, based on the results, NIH official news release said, NIH scientists have begun the development of relevant vaccines to induce the body's immune system to produce a similar antibody response, thus blocking the transmission of HIV stage.
This is the signature of the two studies were 24 and 18. Wu Xueling and Zhou Celebration will respectively become the first of two reports, the study shows they played in real terms.
In the past month, reporters interviewed several times by e-mail Dr. Wu Xueling. She told reporters that since the April 2008 after receiving the issue, and colleagues conducted countless experiments, until August 2009, finally from a 60-year-old gay man of African blood samples of 25 million blood cells, isolated the strongest anti-AI antibody.
Yesterday, Wu Xueling happy to e-mail sent to reporters, said: "We have used the same method, blood samples from another patient in a similar isolated antibody, indicating that antibodies are not unique to a patient
"To know that success, but also to explore what it called"
- Dr. Wu Xueling the strongest anti-AI antibody discovery about the way
Reporters in late July to contact with Dr. Wu Xueling. Meanwhile, her e-mail, reviewed the most potent broad-spectrum they found antibodies against AI research path. The following is an excerpt from one.
Ordered: "successful happy, have failed you have to believe I have done"
April 2008, the entire field of HIV antibody was filled with a kind of pessimism that there is no general sense of broad-spectrum anti-AI virus and monoclonal antibodies in the presence, but this type of antibody response is an effective, to a vaccine to prevent HIV infection necessary. In front of this issue, scientists at a crossroads, the ideal kind of monoclonal antibody, is there? To find or not find ah? In the end, where I Institute of Allergy and Infectious Diseases NIH Vaccine Research Center decided to find, must find!
I and my colleagues, also from China Dr. Li Yuxing has been designated the responsibility for finding the specific work of this antibody. I was actually very difficult, others are not to be found, then what I can find out? However, the nature of scientific exploration is this: What is to explore the ah? Also need to know to successfully explore the what? So I head to the center, I can only dedication and a try. Successful happy, fail you have to believe I have done.
Experiment: constantly subjected to various failure
Separation of the basic steps of antibody determined, but it was harder to implement. Almost every step of the design, and implementation are difficult, especially in single-cell PCR, after the optimized experimental conditions, can only get 25% to 50% positive rate. Cloning and protein expression in vitro process is also the pitfalls everywhere, the success rate of protein expression is often lower than 60%. Even worse, in the final determination of antibody-antigen binding experiment, the no way to know the separation of antibody specificity and specificity of human antibodies in the blood of billions of dollars! I Somatotype often after nearly two months of hard work, carrying out more than a dozen twenty purified antibodies and antigens to do experiments Results blank disc! That means the past two months are "Yang Bailao" all had to start all over again! Several times I looked at those blank test disc, the entire people was almost painful to have to spit it out.
However, can withstand failure is an essential quality of one of the researchers. A person who suffered the collapse of the failure is not possible in the laboratory to stay.
Transfer: Innovation brings success
Transfer in June 2009 to August, we have decided to abandon the routine to do the HIV surface protein antigen labeling approach, which used a central laboratory director Yang Zhiyong vaccine vector and Dr. Zhou Tongqing do alienation protein. The alienation of protein is the basis of the HIV surface protein, through computer simulation and optimization, changing the surface conformation of some proteins, it is no longer a hundred percent of HIV proteins, the HIV proteins and cell receptors The original binding site is preserved. Is so marked and separated from the 29 individual B cells, I successfully isolated 12 antibodies, of which three protein binding with the alienation of the data is correct, then three antibodies is VRC01, VRC02 and VRC03. The final virus and experiments show that they three are broad-spectrum anti-HIV neutralizing antibodies, which VRC01 and VRC02 strain of AIDS coverage to 91%, which far exceeded our expectations!
Impact: Bill Gates is not the hat to eat it?
After several months of data to improve and finishing, our team at the end of January 2010 paper invested in "Science" magazine, and on July 8 online edition of the magazine published. NIH Institute of Allergy and Infectious Diseases that day on the results of doing a special press release. Done a lot of major U.S. media reports, "The Wall Street Journal" We are disclosed in blood samples from the patients used a 60-year-old gay man in Africa, even we ourselves are the first to know.
HIV vaccine research and development from the point of view, this result solves several problems. First of all, the body can not produce such an antibody response is no longer a problem, because the antibody was alive out there. Second, antigen binding antibody VRC01 and the structure has been solved and published, any laboratory can reference this information to design vaccines. Finally, the antibody VRC01 clinical trials can immediately see it and other specific neutralizing antibodies have therapeutic effects in combination. Furthermore, because such success stories, isolated from a patient blood sample more of neutralizing antibodies is no longer a problem. But also because these antibodies against AI vaccines provide specific guidance, vaccination against AI no longer seems out of reach. Bill Gates claimed that because in 2005 "found that an AIDS vaccine within 10 years if I did eat my hat" and open the U.S. media ask: Is the hat to eat it? (Hubei Daily reporter Huang Lei, Zhou Fang)
News source: Sports Network 2010-08-13 10:22 Editor: Ren Zhongjie
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