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美华人科学家成中流砥柱 艾滋病疫苗研究重燃希望
2010年07月19日 09:35 来源：中国新闻网
中新网7月19日电 据美国《侨报》报道，最新一期美国权威的《科学》杂志发表两份报告：美国科学家从艾滋病毒感染者血中分离出两个自然产生的能够中和约9成已知艾滋病毒(HIV)毒株的强力抗体。这项新发现对改良艾滋病疫苗设计和其它病毒性传染疾病的抗体治疗是一个突破性的发展。
在国际艾滋病大会举行之际，这项发现振奋人心，因为它重新点燃了人类成功研制有效艾滋病疫苗的希望。这一研究项目是在美国国立卫生研究院(NIH)过敏与传染病研究所(NIAID)疫苗研究中心主任盖里·纳布尔博士，副主任约翰·麦斯克拉博士和结构生物学实验室主任邝达平博士的主持下完成的，多位华人科学家在其中发挥了中流砥柱的作用，让华人世界为之自豪。
侨报记者特别专访了其中的5位华人科学家，他们讲述了这个突破性发现的来龙去脉，以及在美国从事科研工作的心得体会。
发现攻击艾滋病毒“罩门”
自从人类1980年代初发现艾滋病以来，全球大约已有6000万人感染了艾滋病毒。艾滋病的预防和治疗一直是全球医学科学家屡攻不克的难题，为什么人体免疫系统难以清除艾滋病毒？医学科学界不甚了了。
NIH结构生物学实验室研究员周同庆在接受侨报记者专访时表示，艾滋病毒所以“狡猾”，能够逃避免疫系统监视，一是因为艾滋病毒基因变化比人体正常基因变化快100万倍，人体免疫系统跟不上其变化；其二，艾滋病毒外表有一层与人体正常细胞表层一样的“糖衣”，能够迷惑免疫系统；第三，艾滋病毒的表面蛋白质通过形态变化掩盖一些重要位点，免疫系统难以攻击。因此，周博士认为，攻克艾滋病毒就像武林高手要击败对手，很重要的是找到对方的致命弱点——“罩门”。
周博士解释说，艾滋病毒要感染人体细胞，其表面蛋白质必须首先和人体免疫细胞上的一种叫CD4的受体分子结合。感染人体后的艾滋病毒在人体内不断发生基因突变，从而逃避人体免疫系统的监视。周博士通过多年的研究发现，尽管艾滋病毒千变万化，但它们用来与CD4受体分子结合的最初位点是基本不变的。这个位点正是艾滋病毒的“罩门”。周同庆的这个重要发现作为封面文章，刊登在2007年2月的《自然》杂志上。
2005年开始参与这个探索的病毒实验室研究员李宇星博士说，她们在两个艾滋病毒感染者的血液中发现有针对这个“罩门”的强效抗体存在。李宇星的报告刊登在2007年的《自然》杂志《医学》分册上，引起医学科学界的极大关注。
大海捞针发现最强抗体
发现了“罩门”以后，下一步就是如何将针对CD4结合位点的强抗体以单克隆抗体的方式分离出来。周同庆及其合作者通过分析蛋白质三维结构和电脑辅助设计，对病毒表面蛋白质进行改造，将一些部分巧妙改变，只让那个“罩门”位点保留在原来状态，这个新产生的蛋白质分子可以被用作“探针”，从艾滋病毒感染者的血中寻找能生产强效抗体的细胞。疫苗研究中心载体实验室主任杨志勇参与了“探针”设计的优化过程，并使之变得可行。
病毒实验室研究员伍雪玲与李宇星等同事合作，用这个“探针”在一名60岁黑人同性恋男子的血样中，探测到了能生产针对“罩门”位点的抗体的细胞，并通过复杂的程序，如大海捞针一般，从2500万个血细胞中发现了3个抗体，并进一步分离出两个迄今为止科学界分离的最强有力抗体VRC01和VRC02。它们能够抑制约九成全球流行的艾滋病毒毒株。这是前所未有的高比率。具体负责这项工作的伍雪玲说，这些抗体的抗病毒作用“大大超过预期”。此前加州一个研究所 2009年发现的抗体最多能中和近80%的病毒株。
接着，周同庆通过晶体结构分析，发现抗体VRC01精确地结合在艾滋病毒表面蛋白的那个“罩门”位点上，这就是它之所以那么有效的原因。这项研究为打击艾滋病毒找到了座标，使得研制艾滋病疫苗的目标更加明确。
事实上，NIH的此前发布的新闻说：基于这些发现，NIH的科学家们已经开始初步的疫苗设计，以期诱导人体免疫系统产生类似VRC01的抗体反应，从而有可能抑制全球范围内绝大部份艾滋病毒的传染。
研制疫苗仍有雄关漫道
长期从事艾滋病毒和抗体研究的伍雪玲在接受侨报记者专访时表示，2008年之前，尽管许多实验室都在分离艾滋病抗体，但一直没有发现有效的、广谱的抗体，甚至有著名的实验室宣称“没有广谱单克隆抗体的存在”，这对希望利用抗体来研制艾滋病疫苗的科学家而言，无疑是信心上的打击。
据杨志勇介绍，上世纪80年代中期到90年代中后期，科学家们一度尝试从人体B细胞中寻找抗体来研制艾滋病疫苗，但屡屡无功而返。90年代中后期到2008年之前，科学家们转向试图诱导人体内产生T细胞来杀死受感染细胞的途径来研制艾滋病疫苗，并在猴子身上进行实验，发现这种疫苗虽不能阻断感染，但能抑制疾病的发展。经过多个实验室的动物实验验证，美国默克公司2004年底率先开始进入2期临床试验，但2007年9月，初步试验结果显示，该疫苗并不能保护高危人群免受艾滋病毒感染，有些试验者反而容易感染艾滋病毒。科学家们顿时陷入迷茫，开始重新回到通过自然产生的抗体来研发艾滋病疫苗的道路上。
杨志勇表示，NIH这个发现首次证明了人体内可以自然产生超强中和能力的抗体。这些抗体的发现，同时为艾滋病疫苗研究人员展示了艾滋病毒的最薄弱、最原始的结合位点。
主流媒体在报道这个发现时，纷纷使用了向成功研制艾滋病疫苗“迈出重大一步”的字眼。NIH疫苗研究所中心主任盖里.纳布尔博士说：“过去十年我从来没有像今天这么乐观过。”欣喜和乐观之余，该研究项目主管之一邝达平博士却表达了谨慎之情。他对侨报记者说，这个发现就好比从芝加哥到纽约有500英里的路，刚路过一个路标，上面写着距离纽约还有250英里，这说明你已经走过了长路，方向是正确的，但毕竟还有250英里要走。
邝达平说，这个发现虽然对防止艾滋病的感染目前还不具有重大意义，但揭示了成功研制疫苗并非遥不可及。邝达平认为，要研制有效的能用于人体的艾滋疫苗，至少还有三步要走：第一，现已发现的抗体必须能产生于广泛的人群，而不只是个别人。第二步，必须对达到这么高中和率的抗体生成的过程有更深入的了解。第三步，要有正确的触发因素，能制造出够多的抗体，然后用于动物实验和临床实验。邝达平估计，走这三步大约需要8到10年的时间，而临床试验是否成功，则决定疫苗是否成功，这个就不好预测了。
华人科学家居功至伟
《科学》杂志最新发表的这两份报告，其中一篇的第一作者是周同庆，另外一篇的共同第一作者是伍雪玲、杨志勇和李宇星三人。在两篇署名的各自24位和18位作者中，华人科学家的名字分别占8位和10位，其中多数人是从中国大陆赴美留学并工作的科学家。
出生在美国的华裔科学家邝达平高度赞赏华人科学家做出的“实质性”贡献。他说，虽然有这么多作者，但一般来说， 署名前三位的作者可能完成整个研究的至少75%的实际工作。
周同庆从武汉大学毕业后，在中科院动物研究所拿到博士学位，1995年赴美，在密歇根州的韦恩州立大学做博士后，2001年到NIH工作，一直致力于以结构生物学来研究艾滋病毒及其抗体。
伍雪玲从武汉同济医科大学毕业后，1996年到美国阿拉巴马州立大学伯明翰分校攻读博士，从事艾滋病的抗体分析，后又到西雅图的弗雷德·哈钦森癌症研究所做博士后，着重研究艾滋病毒，2006年进入NIH工作，正好使其病毒与抗体的知识在实用性的研究项目中得以结合。
杨志勇1984年从复旦大学化学系毕业后在中科院上海生化研究所工作了6年，1990年赴美后先在密西根大学医学中心从事基因治疗研究工作，并在1999年进入NIH工作至今，现任疫苗研究中心载体实验室主任。
李宇星从四川大学遗传学专业毕业后，1992年到美国衣阿华州立大学攻读遗传学博士，2001年进入NIH工作后一直从事艾滋病疫苗的研究。
他们其实是NIH众多华人科学家的缩影。据了解，华人科学家在NIH所有科研人员中占有较大比例。这些华人科学家和其他族裔的科学家一道，在美国比较优越的科研条件下和相对完善的制度环境中，辛勤工作，事业有成，为人类健康事业做出贡献。
科学无止境只要肯登攀
周同庆说，做科学研究要有韧性，耐得住寂寞，比如前几年为了进行这项研究，他没有发表过重要论文，但现在成功了，一篇论文可能抵得上10篇普通论文。另外，科学家永远不要放弃好奇心，要在前人已经做过的事情的基础上，独辟蹊径，不断创新。要完成重大的科研项目，团队合作精神必不可少。
伍雪玲回忆起两年前病毒实验室主任约翰·麦斯克拉把寻找抗体的重任交给她时，她感到犹豫，因为别的实验室做了很多年没能发现，而自己做犹如在干草堆里找针，成功的希望很渺茫。抱着“不成功便成仁”的决心接过老板的重托，伍雪玲对侨报记者说，从2008年4月到2009年8月，她经历了无数次的失败，却一次次地变得更有信心。2009年8月当她发现了强抗体，并把结果告诉正在外地出差的老板时，电话那头，老板的声音激动得有些颤抖。伍雪玲说，这个发现再次告诉我们，自然界往往会超过你的预期，科学家不应满足于前人的教科书和结论，要不断发问，向自然界学习。
自称平时都争取准时下班的李宇星参与这个研究后，有时候不得不一天在实验室里呆14、15个小时。她强调，科研要有严谨认真的态度和一丝不苟的精神，要与同事在密切合作的过程中，多切磋，多交流，取长补短，激发灵感。
几位科学家不约而同地称赞美国的科研环境。他们认为，美国科研体制比较合理，人际关系简单，科研条件和待遇比较好，科学家能够专心致志地工作；美国的学术环境也比较纯净，真正有才干、能钻研的人容易脱颖而出。
杨志勇指出，华人科学家来到美国后，一要过好语言关，二要学会与他人和谐相处。也许刚来时会遭遇一些困难，但这两关过了，在相对公平的环境中，华人科学家还是能够如鱼得水的。(余东晖)
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Chinese scientists have become the mainstay of the U.S. AIDS vaccine research renewed hope
At 09:35 on the July 19, 2010 Source: China News Net
BEIJING, July 19, according to Xinhua, "Chinese Press" reported that the latest issue of the authority of the United States "Science" magazine published two reports: U.S. scientists from the blood of HIV isolated from two naturally occurring to the peace 9 percent of known HIV (HIV) strains of powerful antibodies. The new findings on improved AIDS vaccine design, and other viral sexually transmitted diseases, antibody therapy is a breakthrough development.
Held at the occasion of the International AIDS Conference, this discovery is exciting because it re-ignited the successful development of an effective AIDS vaccine human hope. This research project is in the United States National Institutes of Health (NIH) Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center Director Dr. 盖里纳布尔, deputy director of the 约翰麦斯克拉 Structural Biology Laboratory Director Dr. Ping Kwong up completed under the auspices of Dr., a number of Chinese scientists played a pillar of strength for the Chinese world feel proud.
China Press reporter an interview with 5 of them Chinese scientists, they talk about the ins and outs of this breakthrough discovery, and engaged in research work in the United States and experience from.
Found to attack HIV, "Achilles Heel"
Ever since mankind discovered in the early 1980s, AIDS has been about 6,000 million people worldwide infected with HIV. AIDS prevention and treatment of medical scientists has been the world not be able to repeatedly attack the problem, why the human immune system is difficult to remove the HIV virus? Not care about the medical scientific community.
NIH Structural Biology Laboratory researchers accept the newspaper's reporters Week Celebration in the interview, said that HIV so "cunning" to evade the immune system monitoring, first, because the HIV genetic changes faster than changes in the human body 100 times the normal gene, the human immune system keep up with the changes; Second, the HIV surface layer of the surface of normal cells with the human body as a "sugar" can confuse the immune system; Third, the surface protein of HIV shape change through a number of important sites covered, the immune system is difficult to attack. Therefore, Dr Chow that captured HIV as martial arts master to beat opponents, it is important to find the Achilles heel of the other side - "Achilles Heel."
Dr Chow explained that the HIV virus to infect human cells, the surface protein must first and immune cells called CD4 receptor of a molecule. Human cases of infection of HIV in the body mutations continue to occur, thereby evading the immune system of surveillance. Dr Chow through years of research found that while HIV changing, but they used to CD4 receptor molecules and the initial position is basically unchanged. This site is the HIV virus, "Achilles Heel." Week Celebration of this important discovery as a cover story, published in February 2007 of "natural" magazine.
2005 involved in the exploration of the virus, said a researcher in Dr. Li Yuxing, their HIV-infected people in the two found in the blood for the "Achilles Heel" of the existence of powerful antibodies. Somatotype report published in 2007, "Nature" magazine "medical" volumes, the cause of great concern to medical science.
Needle in a haystack find the strongest antibody
Found the "Achilles Heel", the next step is how to address the strong CD4 antibody binding sites to monoclonal antibodies separate ways. Week Celebration and its partners through the analysis of protein three-dimensional structure and computer-aided design, transformation of the virus surface proteins, some of the subtle changes in some, only to the "Achilles Heel" sites remain in the original state, this new protein can be produced as a "probe" from the blood of HIV can be produced in the search for potent antibody cells. Vaccine Research Center, Laboratory Director Yang Zhiyong carriers participated in the "probe" the design optimization process and make it feasible.
Virus Laboratory researcher Wu Xueling and Li Yu magnitude colleagues to use this "probe" in a black gay man 60 years in blood samples, to detect the energy production for the "Achilles Heel" sites of antibody cells, and through a complex process such as needle in a haystack general, from 25 million blood cells found in three antibodies, and further isolate the separation of the two so far the scientific community the most powerful antibody VRC01 and VRC02. They can inhibit some Jiucheng global epidemic of HIV strains. This is an unprecedented high rate. Wu Xueling specifically responsible for this work that the antiviral activity of these antibodies, "far exceeded expectations." Prior to 2009, a research institute in California found that the antibodies and in up to 80% of the virus strain.
Then, weeks of celebrations by the crystal structure analysis showed that antibodies VRC01 precisely combined in the HIV surface protein of the "Achilles Heel" sites, this is the reason for it are so effective. The study found the coordinates of the fight against HIV, AIDS vaccine development goal of making more explicit.
In fact, NIH's previous news release, said: Based on these findings, NIH scientists have started the preliminary of the vaccine 设计 order to induce the immune system Chanshengleisi VRC01 Renti the antibody response, Conger You might inhibit the Global Fan Wei HIV within the vast Bufen viral infections.
Vaccine still impregnable Man Road
Engaged in the study of HIV and antibody told China Press reporter Wu Xueling interview that before 2008, although many laboratories are isolated HIV antibody, but have not found an effective, broad-spectrum of antibodies, even well-known laboratory declared that "there is no broad-spectrum monoclonal antibodies", which wants to use antibodies to develop AIDS vaccine scientists, no doubt the confidence of the blow.
According to Yang Zhiyong description of the last century to the mid-80s in the late 90's, scientists once try to find human B cell antibodies to develop an AIDS vaccine, but often without success. In the late 90's until 2008, scientists have turned to trying to induce the body to produce T cells to kill infected cells in AIDS vaccine development in ways and to experiment on monkeys and found that although the vaccine can not block infection, but can inhibit the development of the disease. Through a number of laboratory animal experiments, the end of 2004 the first U.S. Merck entered Phase 2 clinical trial, but in September 2007, preliminary results showed that the vaccine not protect against HIV infection in high-risk populations, and some test are more easily infected with HIV. Scientists immediately confused and started back through the naturally occurring antibodies to HIV vaccine research and development on the road.
Yang Zhiyong said, NIH found that the first demonstration that the body can naturally produce powerful antibodies in and capacity. The discovery of these antibodies, while for the AIDS vaccine researchers have demonstrated that the most vulnerable to HIV, the most primitive binding site.
Mainstream media in reporting this discovery, have successfully used to develop an AIDS vaccine "a major step toward" the words. NIH Vaccine Research Center Director Frank. Nabl Dr. said: "Over the past ten years I have never been so optimistic as today." Pleased and optimistic, one of the research project director, Dr. Kwong has reached level expression of a cautious love. He told reporters on the China Press, this discovery can be compared to New York from Chicago and 500 miles of road, just across a road sign that says there are 250 miles from New York, this means you have come a long way in the right direction However, there is still 250 miles to go.
Mr Ping said up to this that although the prevention of HIV infection is not yet significant, but revealed the successful development of a vaccine is not out of reach. Ping Kwong up that can be used to develop effective human AIDS vaccine, leaving at least three steps: first, the antibody has been found to produce a wide range of people, not just individuals. Second, must reach such a high rate of antibody and a deeper understanding of the process. The third step is to have the right triggers, can produce enough antibodies, and then used for animal experiments and clinical trials. Kuang Ping is estimated up to take the three steps take about 8 to 10 years, while the clinical trial is successful, determine whether the vaccine is successful, this would predict poor.
Chinese scientists have made enormous contributions
"Science" magazine recently published two reports, the first of which is a week of celebrations, while a co-first author Wu Xueling, Yang Zhiyong and Somatotype three. In the two signed 24-bit and 18 of the respective authors, the Chinese name of the scientist accounted for 8 and 10, most of whom are from mainland China studying in the U.S. and the work of scientists.
Chinese-born scientists in the United States highly appreciates the level reached Kwong Chinese scientists to make a "substantial" contributions. He said that although there are so many authors, but in general, signed the top three of the study may be completed at least 75% of the actual work.
Week Celebration After graduating from Wuhan University, Chinese Academy of Sciences Institute of Zoology, Ph.D. in 1995, the United States, in Michigan's Wayne State University to do postdoctoral work in 2001 to the NIH, has been working to study the structural biology of HIV and its antibody.
Wu Xueling After graduating from Wuhan Tongji Medical University in 1996 to the University of Alabama at Birmingham study for doctorate in HIV antibody analysis, and later to Seattle's Fred Hutchinson Cancer Research postdoctoral, and focused on HIV virus, into the NIH in 2006 to work just to virus and antibodies knowledge in practical research projects to be combined.
Yang Zhiyong, Department of Chemistry in 1984 after graduating from Fudan University in Shanghai Biochemistry Institute of the Chinese Academy of Sciences 6, 1990 after the first U.S. University of Michigan Medical Center in gene therapy research into the NIH in 1999 so far, the current vaccine Research Center Vector Laboratory.
Somatotype Genetics from Sichuan University, after graduating in 1992, the United States to study genetics at Iowa State University Dr., 2001 work into the NIH has been engaged in AIDS vaccine research.
They are actually a microcosm of NIH scientists, many Chinese. It is understood that the Chinese scientists in the NIH all occupy a large proportion of researchers. The ethnic Chinese scientists and other scientists to join research in the United States more favorable conditions and a relatively perfect system environment, hard work, successful careers and contribute to the cause of human health.
Science endless who will try
Week Celebration that do research have toughness, loneliness, like a few years ago For the study, he has not published an important paper, but successful, a paper may be equivalent to 10 ordinary paper. Also, never give up the curiosity of scientists, to their predecessors have done, based on inventive and innovative. To complete a major research project, team spirit essential.
Wu Xueling recalled two years ago, the virus laboratory director 约翰麦斯克拉 to the important task of looking for antibodies to her, she was hesitant, because other laboratory for many years failed to find, and myself as if in a haystack looking for needles, very slim hope of success. Have the "break" the trust of the boss took determination, Wu Xueling on the newspaper's reporter said that from April 2008 to August 2009, she experienced many failures, but time and again to become more confidence. In August 2009 when she found a strong antibody, and the results tell the boss is away on business when the side of the phone, the boss's voice trembling with excitement. Wu Xueling said the discovery once again tell us that nature is often more than you expected, scientists should not settle in the previous textbooks and conclusions, we must continue to ask questions, learn from nature.
Claims for time off work are usually the Somatotype participate in this study, and sometimes had to spend a day in the laboratory 14-15 hours. She stressed that research must be rigorous and meticulous attitude of the spirit of close cooperation with colleagues in the process, many ideas, expertise and more exchanges, learn from each other, inspired.
Several scientists have unanimously praised the U.S. research environment. They believe that the U.S. research system more reasonable, simple relationships, research conditions and better treatment, scientists can focus their attention; the U.S. academic environment is relatively clean, really talented, able to delve into people tend to stand out.
Yang Zhiyong said Chinese scientists to the United States after they have passed a language barrier, second, learn to live in harmony with others. Maybe some of the difficulties encountered when first came, but after two off in a relatively level playing field, the Chinese scientists is to look like a duck's. (Yu Donghui)
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