艾滋病疫苗为何“千呼万唤不出来”———清华大学教授张林琦细说艾滋病及疫苗知识

艾滋病疫苗为何“千呼万唤不出来”———清华大学教授张林琦细说艾滋病及疫苗知识
作者：本报记者王晓晶实习生吴佩   11-28 09:49:42
　　自从1981年艾滋病被确认，迄今已过去20多年了，为何艾滋病疫苗这一对抗传染病最有效的武器却“千呼万唤不出来”，日前，清华大学艾滋病综合研究中心教授张林琦就艾滋病与艾滋病疫苗的有关知识进行了深入浅出的讲解。
　　艾滋病病毒的高变异性是研发疫苗的最大障碍
　　张林琦教授拿着一张形如树枝的示意图说：这是艾滋病病毒遗传与变异图，艾滋病病毒分为两大类，1型和2型，其中1型病毒又分为3个组，M、N、O组，M组内又分为A、B、C、D等11个亚型。艾滋病病毒是RNA病毒，没有校读活性，在每一次扩增过程中，都会出现一些错误的核苷酸，从而导致整个病毒的基因组较复制之前出现大量的变化。
　　“‘变’是艾滋病病毒的生存法则，使其可以抵御人体免疫反应或药物。”张林琦说，艾滋病病毒的高变异性是研发疫苗的最大障碍。他还指出，不同地区的艾滋病病毒是不同的，如在美国猖獗的病毒与在中国猖獗的病毒遗传特点和性质不同，但这些不同病毒相互之间可以重组，这种多变性给研制疫苗带来了非常大的挑战。
　　艾滋病病毒与免疫系统的“较量”
    艾滋病病毒进入人体内到底是怎么运作的？张林琦教授介绍说：艾滋病病毒侵袭的主要是人体免疫系统的一种重要免疫细胞———CD4细胞。早期艾滋病毒进入人体后如入无人之境，病毒在玩命地复制，到达一个非常高的顶点。然后，我们的免疫系统看到了病毒，开始抑制病毒。免疫系统有一定缺陷，不能将病毒扼杀在摇篮中，只有当病毒复制到一定程度，才能检测到，并且只能抑制病毒复制，没有能力清除病毒。到了后期，免疫系统与病毒经过较量之后，免疫系统消亡殆尽，病毒数量剧增。
　　为什么免疫系统不能清除病毒？张林琦解释说，这还是由于病毒的变异性。当我们产生免疫反应时，此时的病毒早就换了“一张脸”，我们的免疫反应都是跟着病毒跑，永远处于被动挨打的局面。
　　由于人体中的CD4系统是主要被侵袭的对象，所以CD4细胞的数量是衡量人体健康状况、特别是衡量艾滋病病毒感染病人健康状况的重要指标。一般正常人CD4细胞每立方毫米为500个到1600个，当这一数量下降为200个时，艾滋病感染者就发展成了艾滋病病人。
　　创新型艾滋病粘膜疫苗值得期待
    作为我国艾滋病疫苗研究的中坚力量，张林琦教授说，当前关于艾滋病的很多基础性研究需要继续做，很多事情还没有搞清楚。比如艾滋病病毒到底是怎么来的，再比如，艾滋病病毒是怎么进入人体细胞并进行复制的，中间的很多细节还不知道。仅仅因为找到了病毒生命周期的几个关键部位，在过去十几年来，人类就已经研发出了20-30种抗艾滋病病毒药物。
　　他还指出，免疫系统有很多特点，也没有被充分利用。张林琦解释说：如“敌我分明”，免疫系统对自身的组织细胞认得很清楚；“打击目标清楚”，病毒侵入后，免疫系统会对其进行全方位打击；“记忆犹新”，对病毒永不忘记。他指出，如果对免疫系统能完全研究清楚，或许能有效地找到抗艾滋病的药物或研发出相关疫苗。
　　张林琦说，历时10年而失败的默克实验显示，单纯以诱导T细胞反应的疫苗策略不足以阻断艾滋病病毒的性传播。由于人体粘膜表面是抵抗艾滋病病毒的第一道防线，我国的创新疫苗策略是粘膜疫苗，通过靶向粘膜免疫策略诱导体内高效抗艾滋病病毒的粘膜免疫反应。据了解，这一研究在2009年世界艾滋病疫苗大会上得以报告，并引起关注。专家还指出，在还没有研制出可有效预防艾滋病的疫苗前，切断传播途径是艾滋病防控中最切实可靠并行之有效的工作。

稿件来源：农民日报责任编辑：蔡薇萍
AIDS Vaccine why "after a long not come out," --- Tsinghua University Zhang Linqi elaborate on the knowledge of AIDS and vaccines
Author: trainee reporter WANG Xiao-jing Wu Pei-fu 11-28 09:49:42
Since 1981, AIDS has been confirmed so far in the past 20 years, why an AIDS vaccine that the most effective weapon to combat infectious diseases is "not come out after a long" a few days ago, AIDS Research Center of Tsinghua University, Professor Zhang Linqi on HIV and AIDS knowledge about the vaccine had to explain in simple terms.
The high variability of HIV is the biggest obstacle to developing vaccines
Professor Zhang Linqi holding a schematic form, such as branches, said: This is the AIDS virus heredity and variation diagram, HIV is divided into two categories, type 1 and type 2, in which a virus is divided into three groups, M, N, O group, M group is further divided into A, B, C, D in 11 subtypes. HIV is a RNA virus, there is no proof-reading activity, in every amplification process, will have some errors nucleotides, resulting in the entire viral genome copies than before a large number of changes.
" 'Change' is the survival of HIV-law so that it can resist the human immune response, or drugs." Zhang Linqi, said the high variability of HIV is the greatest obstacle to developing vaccines. He also noted that different regions of the AIDS virus is different, such as in the United States rampant viruses and virus rampant in China, the genetic characteristics and different in nature, but among these different viruses may be recombinant, such variability has brought to the development of vaccines a very big challenge.
AIDS virus and the immune system's "contest"
AIDS virus enters the human body in the end how the work? Professor Zhang Linqi said: AIDS virus attacks the body's immune system is mainly an important immune cells --- CD4 cells. Early HIV virus enters the human body, such as unhindered, the virus replicated in your life and reached a very high peak. Then we see the immune system with a virus, began to suppress the virus. There are certain deficiencies in the immune system and can not be strangled in the cradle of the virus only when viral replication to a certain level in order to detect and can only inhibit viral replication, not able to clear the virus. A later stage, the immune system and viruses through the contest, the demise of the immune system and exhausted, dramatic increase in viral load.
Why does the immune system can not clear the virus? Zhang Linqi explained that this is due to the variability of the virus. When we generate an immune response when the virus has long been replaced at this time, "a face", we are following the immune responses to the virus to run, never beaten in a passive situation.
As the body of the CD4 system is the main target being hit, so the number of CD4 cells is a measure of human health conditions, particularly HIV-infected patients to measure an important indicator of health status. Generally normal CD4 cells per cubic millimeter of 500-1600, when the number fell to 200, the HIV-infected persons developed into AIDS patients.
Innovative HIV mucosal vaccine worth the wait
As the backbone of China's AIDS vaccine research, Professor Zhang Linqi said that the current definition of AIDS, a lot of basic research needs to continue to do so, a lot of things not yet clear. Example, how the AIDS virus in the end come, then, for example, how the AIDS virus to enter human cells and reproduce itself in the middle of many of the details do not know. Merely lifecycle because of the virus found in several key positions, in the past 10 years, humans have developed out of 20-30 kinds of anti-HIV drugs.
He also noted that there are many features of the immune system and has not been fully utilized. Zhang Linqi explained: such as "polarization", the immune system to recognize its own tissue cells is very clear; "clear targets," viruses, the immune system against its all-round; "remember" the virus Wing do not forget. He pointed out that if research on the immune system will be fully aware that might be able to effectively find the anti-AIDS drugs or vaccines developed related.
Zhang Linqi that lasted 10 years, experiments showed that Merck failed, simple to induce T-cell response to vaccine strategies not block the sexual transmission of HIV. As the human mucosal surface is against the AIDS virus first line of defense, our innovative vaccine strategy is to mucosal vaccines, mucosal immunization strategy by targeting and efficient in vivo induction of anti-HIV mucosal immune response. It is understood that this research in 2009, World AIDS Vaccine Conference to be reported, and cause for concern. Experts also pointed out that developed in the absence of a vaccine effective against AIDS, before the cut off the transmission of AIDS prevention and control of the most effective and reliable and effective work.

Source: Farmers Journal Editor: Cai Wei-ping