本报记者 袁志勇 综合报道

这是当年默克公司艾滋病疫苗临床试验的海报，但试验失败了。 （图片来自《科学》网站）

    这是一种新的解释。实际上，为何无论是现行的药物，还是自身的免疫，或是疫苗，仍还没有一种有效的方法可以根除体内的艾滋病病毒？

    细胞给病毒提供藏身之所 药物无效？

    和其他病毒感染不一样，艾滋病病毒进入体内后是以免疫细胞为对象，又以被感染的免疫细胞为供体感染新的免疫细胞。

    “如果艾滋病病毒进入潜伏期，病毒潜伏在免疫细胞中，不发生复制作用，这有可能导致药物对其无效。”大卫·巴尔的摩研究团队的成员Sigal表示。

    这也是医学界的推断：受感染的免疫细胞成了艾滋病病毒的藏身之所，药物难以对其进行有效控制。

    但大卫·巴尔的摩研究团队有了新的发现：已感染细胞来侵害健康细胞，这种细胞间传播对药物不敏感。

    据介绍，艾滋病病毒在血浆中移动，遭遇免疫系统细胞（T细胞）时，对其传染，称为无细胞传播方式；同时，病毒以被感染的免疫细胞作为媒介在细胞间传播。一旦发现未受感染的免疫细胞，便将病毒传染给该细胞，这是艾滋病病毒的细胞间传播方式。

    研究人员发现，通过无细胞传播方式感染的细胞在抗病毒药物作用下，数目急剧下降，但即使在大剂量药物的作用下，通过细胞间传播感染的细胞却只是缓慢减少。

    然而，研究人员并没有给出明确的答案揭示其中的机理，他们只是肯定的表示：确定病毒的细胞间传播是否导致艾滋病病毒库的产生，对研究治疗方案尤为重要。

    自身难以清除 免疫失效？

    如果把免疫系统当作人体自身的“卫士”，那外来的细菌、病毒就是“入侵者”，但如果自身的“卫士”都中毒了，甚至成为传播疾病的“帮凶”，你还能指望他们正常的发挥作用吗？

    艾滋病病毒进入人体后，会攻击一类免疫细胞，导致它们遭到完全破坏，甚至成为传播病毒的载体。免疫系统出现了问题，自然就难以清除病毒了。

    当然，并不是所有的免疫细胞都会失效，健康犹存的免疫细胞，依然在忠实的执行自己的“职责”，它们会分泌一种杀灭艾滋病病毒的物质——艾滋病病毒抗体。

    可惜的是，这些抗体并不能直接和某些细胞内的病毒直接接触，这些细胞内的病毒自然就逃过了抗体的查杀。此外，艾滋病病毒会发生一定程度的变异，这样，原来专门产生的针对性抗体自然就不能识别变异的病毒了，免疫又一次失效了。

    还有一种情况就是，在病毒的潜伏期，病毒会以某种形式整合入健康细胞基因组中，免疫系统会把病毒忽略，当成自身正常的部分。这也是为何在潜伏期，有时检查中会出现抗体阴性的结果。

    疫苗预防 难以实现？

    近几年，国外对艾滋病疫苗的研究举步维艰。

    尽管美国前总统克林顿就预言过2007年根治艾滋病的疫苗将研制成功。但是，由于无法攻克艾滋病病毒结构变异性强的特点，该预言不幸付诸东流。

    2007年9月中旬，默克制药公司宣布，其耗时10年研制的艾滋病疫苗中期临床

    试验失败；同年9月底，美国国立卫生研究院（NIH）在最后一刻决定：停止一项耗资达1.3亿美元的艾滋病疫苗试验。

    对艾滋病疫苗界来讲，当年默克的试验失败是一场灾难性的打击。因为默克的疫苗被认为是最有希望的艾滋病疫苗，然而，该试验的一项中期安全分析显示，该疫苗既无法保护志愿者免遭致命病毒的侵袭，也不能减少艾滋病病毒感染者体内的病毒数量，甚至一些受试者在接种了艾滋病疫苗后变得更容易感染艾滋病病毒。没有人知道这一过程的机理，结果表示，他们也不想再花钱弄懂这一机理，疫苗被停止了，前期的投入打了水漂。

    2009年9月，国外的研究人员研发出一种新艾滋病疫苗，其可以使接种者的感染风险降低31.2%。整个实验有1.6万人参加，耗资1.05亿美元。但业内称：31.2%实际是比较低的保护率，乙肝疫苗大约能达到85%—90%的保护效果，这才是疫苗保护率的正常水平。

    2011年5月，《自然》杂志网站登载报告称，美国俄勒冈卫生科学大学等机构研究人员研发的疫苗能在一些恒河猴身上有效抑制SIV病毒的活动。艾滋病的全称是获得性免疫缺陷综合征（AIDS），它在人群中由人类免疫缺陷病毒（HIV）引起，而在猴子当中由猴免疫缺陷病毒（SIV）引起。尽管报告认为，此次研究成果是艾滋病疫苗研发中的一个重要进展，将有助于研发用于人类的艾滋病疫苗。如果说这是一条让人兴奋的消息，但一些专家却给大家泼了冷水，他们明确指出，将这一方法应用于人类还需要解决的主要问题是如何确保用于制造疫苗的病毒不会带来副作用。

    其次，疫苗研究的一个重要问题是：怎样设计试验？

    动物试验也许容易解决，但临床试验怎样设计呢？选择什么样的人群？让他们怎样暴露在艾滋病病毒下？更多的人，担心这种试验有可能产生混乱。

    也许西方不亮东方亮，“十一五”期间，中国16个国家重大科技专项之一的“艾滋病和病毒性肝炎等重大传染病防治”中，创新性艾滋病疫苗已完成Ⅰ期临床试验，这或许能带来些许希望。

    ———————■相关链接 ———————

    基因变异 他们天生对HIV免疫

    蒂莫西·雷·布朗（Timothy Ray Brown）一定是2010年最引人注目的病人。他曾经被艾滋病纠缠了整整10年。2010年12月8日，一个由德国三所大学医学部研究人员组成的七人小组在著名科学杂志《血液》上发表在线论文称：研究结果证明这个病人的艾滋病被治愈了。

    这是因为布朗接受了一位具有CCR5△32型基因的人的骨髓捐献。移植手术后，新的细胞对艾滋病病毒免疫。

    原来HIV要通过免疫细胞上的称为CD4受体和CCR5或CXCR4的两个辅助受体，才能入侵免疫细胞。如果人体基因发生变异，导致产生CCR5-△32变异，大多数HIV毒株就失去门路，无法感染细胞。一般来说，一般地，人体中每个基因都有两个副本。拥有一个CCR5-△32变异副本，人对HIV的抵抗力就会增强，即使受到感染，发病过程也会比普通人缓慢。如果有两个变异副本，就基本上对HIV免疫了（并非完全免疫，有两个变异副本而仍死于艾滋病，这样的例子虽然罕见但的确存在，有的HIV毒株可能并不需要以CCR5为通道）。

    然而，黄种人中少有具有CCR5△32型基因的人，非洲土著、东亚、印度等人群里都不存在这个变异，它是欧洲人特有的。在欧洲不同地区，它出现的频率也不一样，其中以北欧高达14%，地中海沿岸则仅为2%。平均说来，约有10%的欧洲人拥有一个变异副本，1%的人拥有两个副本。

    看来身为中国人的你我，很难出现这种变异，更别提和你配型一致的骨髓的概率了。

艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复

图示∶2011年5月正式出版的《中国特色医疗金鉴》登载的刘君主任及其机构事迹

慢性艾滋病早期中医药治疗保障生命论证 红津液饮料面世 或将能预防艾滋病 更多来源∶新浪商业登载 http://vic.sina.com.cn/news/27/2010/1231/26801.html TOM新闻登载 http://post-social.news.tom.com/s/63000AD83310.html 中国青年网 健康频道 http://news.youth.cn/jk/201012/t20101231_1447239.htm  环球时报-环球网 http://news.163.com/10/1231/15/6P8B7PTU00014JB6.html  环球网 http://china.huanqiu.com/hot/2010-12/1390550.html

 

 

Why can not eradicate HIV
Posted: 2011-08-30 | Author: Yuan Zhiyong
http://www.stdaily.com 2011 年 08 月 30 MVP: Science and Technology Daily Author: Yuan Zhiyong
  The reporter Yuan Zhiyong Roundup



That is a Merck HIV vaccine clinical trials posters, but the experiment failed. (Photo from "Science" website)

    August 17, in "Nature" magazine published a Caltech biology professor, Nobel laureate David Baltimore (David Baltimore) research team led by an article, they found that HIV infection may have been used cells to close to healthy cells, enabling large quantities of virus spread, which may be HIV anti-retroviral drugs after successful treatment, in a few infected cells can still survive reasons.
    This is a new interpretation. In fact, why both the existing drugs, or their own immunity, or vaccine, is still not an effective way to eradicate HIV in vivo?

    Cells for the virus hid the drugs ineffective?

    And other viral infections is not the same, after HIV enters the body as an object based on immune cells, on the infected immune cells infected with the new donor immune cells.

    "If the AIDS virus to enter the incubation period, the virus hidden in immune cells, replication does not occur, and this may lead to drug them invalid." Study team member David Baltimore, Sigal said.

    This is also inferred the medical profession: the immune cells become infected with HIV hiding place, drugs difficult to be effectively controlled.

    However, David Baltimore, a new research team found that: against the infected cells to healthy cells, which spread among the drug is not sensitive.

    According to reports, HIV in the plasma to move, hit the immune system cells (T cells) when their infection, known as cell-free transmission; the same time, the virus in infected immune cells as the medium of communication between cells. Once uninfected immune cells, they put a virus to the cells, which are cells of HIV transmission.

    The researchers found that cell-free transmission by infected cells in the antiviral effect, the number declined sharply, but even large doses of drugs under the action of cell-cell spread by infected cells, but only slowly decreased.

    However, researchers did not give a clear answer to reveal the mechanism, they are just in the affirmative: to determine whether the virus spread between cells generated virus that causes AIDS, the study treatment is particularly important.

    Itself difficult to remove immune failure?

    If the body's own immune system as a "guardian", and that foreign bacteria, virus is the "invaders", but if their "guards" are poisoned, and even spread the disease to become an "accomplice", you can expect them to normal role?

    HIV enters the body, it will attack a class of immune cells, causing them to have been completely destroyed, even as the carrier of the virus spread. Immune system problems, naturally, difficult to remove the virus.

    Of course, not all immune cells will become invalid and health still remain immune cells, is still in the faithful implementation of their "duties", they secrete a substance to kill the AIDS virus - HIV antibodies.

    Unfortunately, these antibodies do not directly and some direct contact with the virus within cells, these cells the virus naturally escape antibody killing. In addition, the AIDS virus will occur a certain degree of variation, so that the original special produced by targeted antibody does not recognize the natural variability of the virus on the immune once again ineffective.

    Another case is that in the virus's incubation period, the virus will be some form of integration into the genome of healthy cells, the immune system ignores the virus, as a normal part of their own. This is why the incubation period, there will sometimes check in antibody-negative results.

    Vaccine is difficult to achieve?

    In recent years, AIDS vaccine research abroad difficult.

    Although the former U.S. President Bill Clinton predicted that over 2007 will cure AIDS vaccine developed. However, because HIV can not overcome the structural variation in the characteristics of strong, unfortunately the prediction down the drain.

    In mid-September 2007, Merck announced that its 10-year time-consuming medium-term clinical development of AIDS vaccine

    Test failed; the end of September the same year, the U.S. National Institutes of Health (NIH) at the last minute decision: to stop a $ 1.3 billion AIDS vaccine trials.

    AIDS vaccine industry is concerned, when Merck's test failure is a catastrophic blow. Because Merck's vaccine is considered the most promising AIDS vaccine, however, the trial of an interim safety analysis showed that the vaccine can not protect volunteers from both deadly viruses, can not reduce HIV infection in vivo viral load, and even some of the subjects of AIDS vaccine in the vaccination becomes more susceptible to HIV. No one knows the mechanism of this process, the results that they do not want to spend money to understand this mechanism, the vaccine was stopped early than wasting.

    September 2009, foreign researchers developed a new AIDS vaccine, the vaccine can reduce the risk of infection by 31.2%. There are 1.6 million people participated in the experiment, a cost of $ 105 million. But the industry said: 31.2% effective rate of protection is relatively low, hepatitis B vaccine can reach about 85% -90% of the protective effect, this is the normal level of vaccine protection rate.

    May 2011, "Nature" magazine posted on the website report, Oregon Health Sciences University and other U.S. institutions researchers developed the vaccine in some rhesus monkeys who can effectively suppress SIV viral activity. AIDS full name is Acquired Immune Deficiency Syndrome (AIDS), it is in the crowd by the human immunodeficiency virus (HIV) causes, in which the monkeys from the simian immunodeficiency virus (SIV) cause. Despite the report that the AIDS vaccine research is an important progress in development, will contribute to research and development for human AIDS vaccine. If this is an exciting news, but we gave some experts poured cold water on, they clearly point out that this approach will be applied to humans also need to address the main problem is how to ensure for the manufacture of the vaccine virus does not take to side effects.

    Secondly, the vaccine is an important question is: how to design experiments?

    Animal testing may be easy to solve, but how to design clinical trials it? Choose what kind of crowd? So how they under exposure to HIV? More people worried about this test may produce confusion.

    Perhaps the West does not shine Dongfang Liang, "Eleventh Five-Year" period, China's major science and technology in 16 countries, one of the "major infectious diseases such as AIDS and viral hepatitis prevention and treatment", the innovative AIDS vaccine has completed Phase Ⅰ clinical trial, which may be able to bring a bit of hope.

    ------- ■ Links -------

    Genetic variation they are born to HIV immunity

    Timothy Xilei Brown (Timothy Ray Brown) must be the most compelling of 2010 patients. He had been struggling for a whole 10 years of AIDS. December 8, 2010, a German three University School of Medicine researchers in seven groups in the prestigious scientific journal "Blood," published online papers said: The results demonstrate that the patient was cured of AIDS.

    This is because Brown has accepted a CCR5 △ 32-type genes of the human bone marrow donation. After the transplant, the new immune cells to HIV.

    The original HIV through the immune cells called CD4 receptors on the CXCR4 and CCR5 or both coreceptors to invade immune cells. If the human gene mutation, resulting in CCR5-△ 32 mutation, the majority of HIV strains lost opportunities, and can not infect cells. Generally speaking, in general, the human body has two copies of each gene. With a CCR5-△ 32 copies of the variant, people with HIV resistance will be enhanced, even if infected, the incidence process will be slower than the average person. If there are two copies of the variant, it basically immune to HIV (not entirely immune, there are two copies of the variant and still die of AIDS, such examples are rare but do exist, and some HIV strains may not need to CCR5 for the channel).

    However, among the few yellow-type gene with CCR5 △ 32 people, indigenous African, East Asia, India, the crowd did not exist in this variation, it is unique to Europeans. In different European regions, it is not the same frequency of occurrence, of which up to 14% Nordic, Mediterranean, compared with only 2%. On average, about 10% of Europeans have a copies of the variant, 1% of people have two copies.

    It seems the Chinese people as you and I, this variation is difficult to occur, not to mention to you the same type with the probability of the bone marrow.

(Technology News)

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