令人感到恐怖的艾滋病发现25年来，人们一直在努力寻求能够抵抗致病病毒———人体免疫缺乏病毒(HIV)的有效疫苗，以防止艾滋病感染和蔓延。但是，在投入无数人力和物力之后，科学家至今仍然没有获得理想的结果。日前，美国加州理工学院的研究人员在《国家科学院院刊》上撰文表示，疫苗研究进展缓慢或许有多种原因，但至少有一部分应归结于这样一个事实，那就是我们人体中天然的HIV病毒抗体本身不够大，难以有效地中和病毒。
人体中Y型的抗体是中和病毒的最理想抗体，当它们的Y型双臂伸开并几乎在同时抓住目标病毒的蛋白时，就能发挥阻断病毒进入细胞和防止感染等作用。面对HIV病毒，能够阻断感染的抗体将突出在病毒表面的蛋白作为捕捉目标，这些蛋白就如同从病毒膜内长出的尖刺。如果病毒表面两尖刺的距离正好与抗体的臂展(即抗体两臂伸开的距离)相当，那么一个抗体在同一时刻可以也只能抓住(或锁定)两个尖刺。
文章第一作者、加州理工学院生物化学和分子生物物理学研究生约书亚·克莱恩说，抗体的双臂同时锁定病毒后，就使相互作用的能力提高百倍乃至千倍，这种相互作用有时也意味着抗体中和病毒能力的大力提高。他认为，具有双臂的抗体是确保其锁定病毒的天然方法。然而，这种双臂锁定的方式说易行难，至少对HIV病毒来说是这样。
加州理工学院生物学教授、霍华德休斯医学研究所研究人员帕梅拉·比约克曼和克莱恩在论文中介绍了他们对两种不同的单克隆抗体中和HIV病毒能力所完成的研究。两种单克隆抗体均取自HIV感染者，它们分别是抗体b12和抗体4E10。前者能够锁定组成HIV蛋白尖刺上部的gp120蛋白，后者能锁定尖刺下部或茎部的gp41蛋白。
研究人员将两种单克隆抗体按照它们的组成部分进行了分解，并将两者对病毒的锁定和中和能力加以比较。他们发现，正如所期待的那样，单臂的b12抗体中和HIV病毒的有效性低于具有双臂的b12抗体。但是，对于4E10抗体，双臂本版的4E10抗体比单臂的在中和能力上没有多大的优势。
此外，他们还发现，尺寸大的4E10抗体的中和病毒效率低于尺寸小的4E10抗体。这些结果凸显了人们设计疫苗诱导类似4E10抗体时所将面临的潜在障碍。
对于b12抗体，它也存在着自身需要克服的问题。事实上，当更深入分析他们所获得的数据时，研究人员发觉与中和流感病毒的其他抗体相比，即使是具有双臂的b12抗体，它们的双臂要小得多。换句话来说，就是人体天然的抗HIV病毒的抗体在中和HIV病毒效能上比实际应有的要小许多。
追究其中的原因，克莱恩解释说，单个流感病毒表面分布有大约450个尖刺，而同其体积相当的HIV病毒表面的尖刺不足15个。HIV病毒表面尖刺数目少和间距更大的现实，致使出现病毒尖刺距离正好与b12或4E10抗体臂展(12纳米至15纳米)相当的情况成为难题。
克莱恩认为，HIV病毒可能通过进化，逃脱了人体免疫系统用于抵御病毒感染的重要手段。根据掌握的数据，似乎HIV病毒绕开了抗体发挥作用的关键———二价效应。比约克曼表示，新的研究帮助人们认清了在阻止病毒感染时抗体所面临的障碍，同时将有望解释为何人们在开发有效HIV病毒疫苗时情况如此难以琢磨的原因。
诺贝尔获奖者、生物学教授大卫·巴尔的摩认为，克莱恩他们发表的是一篇十分重要的论文，因为文章改变了人们在认识HIV病毒抗体为何效果差这一问题上的关注点。它将人们的注意力带向早已知晓但长期以来又一直被忽略了的双臂抗体攻击。论文说明抗HIV病毒的抗体使用单臂受到了限制，锁定能力差。他表示，应对新研究结果提出的挑战是十分困难的事情，因为研究证实的是几乎所有天然抗HIV病毒的抗体在有效性方面所固有的局限性。
The key to AIDS vaccine research and development difficulties or natural human antibodies to small
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April 27, 2009 Science and Technology Daily
AIDS is found in terror over the past 25 years, people have been trying to find a virus resistant to disease --- the human immunodeficiency virus (HIV) and effective vaccine to prevent infection and the spread of AIDS. However, numerous human and material inputs, the scientists still did not get the desired results. A few days ago, U.S. researchers at the California Institute of Technology in the "National Academy of Sciences," the author said that the slow pace of vaccine research may be a variety of reasons, but at least in part be attributed to the fact that we human HIV virus in the natural antibody itself is not big enough, it is difficult to effectively and viruses.
Y-type body and the antibody is the best virus antibodies, when they open the Y-arms, and almost at the same time to seize the target protein when the virus can play a block to prevent the virus entering the cells and the role of infection. The face of HIV virus, the antibody can block the infection will be highlighted in the HIV surface protein as the capture target proteins from the virus membrane as the spines grow. If the virus surface is the distance between the two spines and outreach arm of the antibody (or antibody with open arms distance) is, then an antibody can be at the same time we can only grasp (or lock) the two spines.
The first author of the article, the California Institute of Technology biochemistry and molecular biophysics graduate student Joshua Klein said that the antibody after the virus lock arms at the same time, which makes the interaction of hundreds or even thousands of times ability, this interaction is sometimes also means that HIV antibodies and to enhance the capacity of the strong. In his view, the antibody has two arms is to ensure that the natural way to lock the virus. However, this way of locking arms easier said than done, at least this is the case for the HIV virus.
California Institute of Technology biology professor, Howard Hughes Medical Institute researchers Pamela Bjorkman and Klein introduced in the paper they are two different monoclonal antibodies and the HIV virus, the ability to complete the study. Two monoclonal antibodies are derived from HIV-infected persons, they are the b12 antibody and antibody 4E10. The former can lock the upper part of the composition of the HIV protein gp120 protein spines, which can lock the lower part or stem spines of gp41 protein.
Researchers in accordance with the two monoclonal antibodies to carry out their part of the decomposition, and both the virus and the ability to lock and to compare. They found, as expected, the single antibody b12 and the HIV virus than with the arms of the effectiveness of the antibody b12. However, the 4E10 antibody, 4E10 antibody arms than the version in the arm and ability, there is not much advantage.
In addition, they also found that large size of the 4E10 antibody and the virus is lower than the efficiency of the small size of the 4E10 antibody. These results highlight the people similar to the design of vaccine-induced antibody 4E10 will face when the potential obstacles.
The b12 antibody, which also has its own issues to overcome. In fact, when more in-depth analysis of the data they receive, the researchers found that influenza viruses with and compared to other antibodies, even with the arms of the b12 antibody, which is much smaller arms. In other words, is the natural human antibodies against HIV virus and HIV virus in the performance than the actual due to the small number of.
Investigated the reason, Klein explained that the distribution of a single influenza virus surface about 450 spines, and with a considerable size, the surface of the HIV virus spines less than 15 months. HIV virus, the number of surface spines and less the reality of a greater distance, resulting from the emergence of the virus coincides with spines or 4E10 antibody b12 outreach arm (12 nanometer to 15 nm) the situation very difficult.
Klein believes that, HIV virus may evolve to escape the body's immune system to ward off an important means of infection. According to available data, it seems that the HIV virus, antibodies play a role in bypassing the key effect of divalent ---. Bjorkman said that the new research to help people get a clear understanding of the antibody to prevent infection when facing obstacles, but is expected to explain why people in the development of an effective HIV vaccine so elusive at the reasons.
Nobel Prize winners, David Baltimore, professor of biology believe that Klein published their paper is a very important, because the article changed the way people in understanding why the effect of HIV virus antibodies difference on the issue of concern. It will bring attention to the already known but also has been a long time ignored the antibodies attack the arms. Thesis that anti-HIV virus has been limited use of one arm, locking poor. He said the new findings deal with the challenges posed by it is very difficult, because research has shown that almost all natural anti-HIV virus in the effectiveness of the inherent limitations.
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