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艾滋病疫苗重燃斗志
2010年02月21日 14:43:43 来源：环球科学
▲小小的胜利：在泰国进行临床试验的艾滋病疫苗，如果说确实产生了保护作用，这种作用也很少，但该试验依然让大家看到了希望。
撰文/凯瑟琳·哈蒙（Katherine Harmon）
漫长的艾滋病疫苗研究经历过无数次不成功的开局，临床试验也一次又一次遭遇挫败，使这个曾经令人充满希望的领域陷入了悲观失望的阴影之中。2009年秋天，随着泰国艾滋病疫苗Ⅲ期临床试验的报道见诸报端，似曾相识的一幕再度出现：一开始媒体纷纷鼓吹疫苗具有保护性效果，使人深受鼓舞，但这种情绪很快就被失望取代，因为重新分析显示，这种保护或许可归因于偶然因素。不过这次失败并未浇灭艾滋病疫苗的全部希望，反而让一些研究者重燃斗志，让他们在与这种致命疾病的抗争中看到了一些新的线索。
在泰国进行的临床试验是迄今为止最大规模的艾滋病疫苗测试，共耗资1.05亿美元，招募了超过16,000名受试者。该试验于2003年启动，2009年9月公布初步结果，表明这种疫苗（由两种已知疫苗药物ALVAC-HIV和AIDSVAX B/E按一定顺序接种而成）在统计学意义上具有轻微的保护作用。不过到了10月，包括多种统计分析结果的报告全文在法国巴黎一次学术会议上一经公布，立即引出了更大的质疑之声。确切地说，受到质疑最多的是这样一种说法——在试验进行期间，注射安慰剂的受试者中有74人感染HIV，注射疫苗的受试者中有51人感染，相比之下，疫苗感染风险降低了31.2%。然而，如果把试验一开始就已经查出感染HIV的7个人（2人在安慰剂组，5人在疫苗组）也包括进来，疫苗的有效性就下降到了26.4%。
美国加利福尼亚州拉霍亚市斯克里普斯研究所的免疫学家丹尼斯·伯顿（Dennis Burton）认为：“这一试验的前前后后还存在着大量不确定因素。”这项试验的受试者都是患病风险中等和偏低的人，比如恪守一夫一妻制的异性恋者，而不是静脉注射吸毒者这样的高风险人群。他还指出，“受试者人数较少”，因此就统计学而言，所谓的保护作用可能纯属巧合。
然而许多研究者依旧确信，这项试验提供了许多可供琢磨的数据。“这项研究贡献了更多的证据，表明艾滋病疫苗有可能研制成功，”泰国临床研究报告的合作者、美国沃尔特里德陆军研究所（Walter Reed Army Institute of Research）的杰罗姆·金（Jerome Kim）说道。（报告全文详见《新英格兰医学杂志》2009年10月刊。）他表示：“这只是我们前进的一小步，虽然不是一个全垒打，但它开启了通往未来研究的大门。”
疫苗研究的支持者还指出，默克公司STEP临床试验的失败让研究者汲取到了宝贵的教训。那项疫苗测试于2007年终止，只进行到Ⅱ期临床试验，但即便如此，也不意味着研究者又重新回到了起点。杰罗姆指出，那项试验揭示了如何才能阻止一些HIV毒株感染细胞，提供的数据还有助于解释泰国试验的结果。2009年11月发表在《美国国家科学院院刊》上的一篇论文，对半途终止的STEP临床试验进行了重新分析。这篇论文警告说，用于向人体各处递送无活性HIV毒株的那种载体［腺病毒（adenovirus），曾在其他成功的疫苗开发中采用过］，实际上会使免疫系统在受到感染时更加脆弱，因为它们会把易于感染的T细胞召集到黏膜（mucous membrane），而这正是性行为发生时最容易受到感染的组织。
找到有效的HIV疫苗，已经成为了一项越来越迫切的任务。尽管新疗法层出不穷，艾滋病仍然是一个绝症。世界上每天大约有7,000人感染HIV，美国每年确诊的新发病例就有66,000例（我国2009年新发感染病例为48,000例）。保护人们不受HIV感染，不仅能够拯救数以百万计的生命，还能极大地降低艾滋病的治疗费用。美国波士顿贝丝以色列女执事医疗中心（Beth Israel Deaconess Medical Center）的拉斐尔·多林（Raphael Dolin）说，疫苗“才是控制这场可怕瘟疫真正唯一的最佳方法”。他还给2009年10月发表的那份泰国试验报告配写了一篇评论。
疫苗的作用是预先刺激免疫系统，教它学会识别目标病原体（pathogen），一旦检测到真正的目标，即可迅速发起攻击。为了抵挡HIV，研究者先引入一种疫苗（ALVAC）来诱导T细胞应答，对免疫系统进行“战前动员”，然后再用另一种疫苗（AIDSVAX B/E）刺激一种抗体应答。在先前针对静脉注射吸毒者进行的Ⅲ期临床试验中，AIDSVAX并未发挥作用。赛诺菲巴斯德公司制造的ALVAC此前从未进行过单独测试。
AIDS vaccine rekindle the fighting spirit
February 21, 2010 14:43:43 Source: Global Science
▲ small victory: In Thailand, AIDS vaccine clinical trials, if indeed had a protective effect, this effect is also minimal, but the pilot is still so that everyone can find hope.
The author / 凯瑟琳哈蒙 (Katherine Harmon)
AIDS vaccine research long after countless unsuccessful start, clinical trials face defeat again and again to make this once promising area of trapped in the shadow of despair. Autumn of 2009, with the Thai AIDS Vaccine Phase Ⅲ clinical trials reported in newspaper re-emergence of familiar scene: the media have begun to advocate a vaccine has a protective effect, people are encouraged, but such sentiments were soon disappointed replaced as the re-analysis shows that this protection may be attributed to causal factors. However, this failure was not extinguished all hope for an AIDS vaccine, but let some researchers renewed fighting will allow them to struggle with this deadly disease to see some new clues.
Conduct clinical trials in Thailand is by far the largest AIDS vaccine trials, a total cost of 105 million U.S. dollars, recruited over 16,000 subjects. The trial was launched in 2003, published in September 2009 preliminary results show that the vaccine (from two kinds of vaccines are known to ALVAC-HIV drugs, and AIDSVAX B / E vaccine made by a certain sequence) in the statistical sense, with a slight protection. However, to 10 months, including a variety of statistical analysis of the full report of the results of an academic conference in Paris, France, on 1 The announcement immediately led to a larger dispute. To be sure, been questioned most often such a statement - during the trial, the subjects in the placebo, 74 people are infected with HIV, the subjects in the vaccine, 51 people are infected, compared with , the vaccine reduced the risk of infection, 31.2%. However, if the test had been found infected with a beginning, HIV-seven individuals (two in the placebo group, five people in the vaccine group) are also included, the effectiveness of the vaccine but dropped to 26.4%.
Scripps in La Jolla, California Institute immunologist Dennis Burton (Dennis Burton) said: "The Ins and Outs of this test, there are still a large number of uncertain factors." The trial by the The subjects were all middle-and low risk people, such as those who abide by the monogamous heterosexual, rather than intravenous drug users, such as high-risk groups. He also pointed out that "a small number of subjects," so the statistics, the so-called protective effect may be purely coincidental.
However, many researchers remain convinced that the experiment provides a number of data available for pondering. "This study contributed more evidence that the successful development of an AIDS vaccine is possible," clinical study in Thailand a partner in the U.S. Walter Reed Army Institute of Research (Walter Reed Army Institute of Research) of the Jerome Gold ( Jerome Kim) said. (The full report see the "New England Journal of Medicine" in 2009 10 issue.) He said: "This is just a small step forward, although not a home run, but it opens the way to the door for future research."
Supporters also noted that vaccine research, Merck STEP trial failed to allow researchers learned valuable lessons. That the termination of the vaccine tested in 2007, only for the Phase Ⅱ clinical trial, but even so, does not mean that researchers have once again returned to the starting point. Jerome pointed out that trials reveals how you can prevent some strains of HIV infected cells, providing data also help explain the test results in Thailand. In November 2009, published in "The United States National Academy of Sciences," on a paper on the halfway STEP termination of the re-analysis of clinical trials. The paper warned that the entire human body is used to deliver the kind of non-active strains of HIV vectors [adenovirus (adenovirus), had other successful have been used in vaccine development], actually make the immune system is infected to be more vulnerable because they would easily infected T-cells called the mucosa (mucous membrane), which is the best sex occurs when the organization vulnerable to infection.
To find an effective HIV vaccine has become an increasingly urgent task. Despite the endless stream of new therapies, AIDS remains a terminal illness. In the world every day there are about 7,000 people are infected with HIV, the United States of new cases are diagnosed every year there are 66,000 cases of (our new infections in 2009 for 48,000 cases). To protect people from HIV infection, not only save millions of lives, but also greatly reduces the cost of AIDS treatment. Boston, Beth Israel Deaconess Medical Center (Beth Israel Deaconess Medical Center) Raphael Dolin (Raphael Dolin), said the vaccine "is the control of this terrible plague really the only best way." He returned in October 2009 test report issued share of Thailand with written commentary.
The role of vaccines in advance to stimulate the immune system, teach it to learn to identify the target pathogens (pathogen), once the real target is detected, you can quickly attack. In order to ward off HIV, the researchers first to introduce a vaccine (ALVAC) to induce T-cell response, the immune system to "pre-war mobilization", and then another vaccine (AIDSVAX B / E) to stimulate an antibody response. In previous intravenous drug users carried out for Phase Ⅲ clinical trials, AIDSVAX did not play a role. Manufactured by Sanofi Pasteur ALVAC alone had never been tested.
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