艾滋病疫苗：非著名科学家研究被忽略

艾滋病疫苗：非著名科学家研究被忽略
2009年12月01日07:56 来源：《科技日报》
　　一项科研成果让艾滋病疫苗研究者从无尽的黑夜中看到一道曙光：美国和泰国研究人员近期联合宣布，他们研发出的一种新型试验疫苗可使人体感染艾滋病病毒的风险降低31.2%。这是自1983年发现艾滋病病毒以来，世界上第一种具有一定免疫效果的艾滋病疫苗。尽管其免疫效果还很有限，但终究实现了免疫效果从无到有的飞跃。

　　然而，在刚刚结束的2009世界艾滋病疫苗大会上，作为目前全球唯一开展活载体疫苗临床试验的研究人员，中国疾病预防控制中心艾滋病首席专家邵一鸣在演讲时说的第一句话是，我们现在的技术路线以及美泰疫苗Ⅲ期临床研究，都是在20年前胡小乐教授的工作基础上发展而来的。遗憾的是，当年，这位“非著名科学家”的观点并没有受到重视。否则，10年前，我们可能就会拿到今天的结果。

　　20年前，非著名科学家的研究被忽略了

　　在百度里输入“胡小乐艾滋病”的词条，其中一项搜索结果是1993年第5期的《生物学通报》，它记录了美国华裔科学家胡小乐研究小组当时的研究进展：“已在短尾猴身上试验成功预防艾滋病的疫苗。所有受试猴子在接受疫苗接种后免疫力都大大增加。接受疫苗的受试猴不仅自身不会感染艾滋病毒，并且也不会成为病毒的载体……”

　　事实上，早在1989年，胡小乐就在论文中提出，可由两种独立使用均无效果的疫苗组成“联合疫苗”，其中第一种纽约株痘病毒活载体负责做初免，进行攻击艾滋病病毒的准备；第二种蛋白类疫苗则充当“助攻手”。这一“初免―加强”的思路被应用在美泰疫苗Ⅲ期临床研究的设计中。然而，胡小乐当时只是美国中等规模药厂施贵宝公司艾滋病疫苗研究首席科学家，其成果并未受到业界的重视。

　　那些能够左右学术方向的大科学家按照理论科学的思维，想当然认为死载体要比活载体安全性更好，几乎整个艾滋病疫苗领域都在开展以非复制型载体为主的死疫苗和以T细胞免疫为主导的研究。

　　胡小乐的非主流研究声音被淹没了。1997年，美国默克公司花重金启动艾滋病疫苗计划时，使用的也是非复制型腺病毒载体死疫苗，然而，花费数亿元的计划在2007年被迫中止。临床试验结果显示，疫苗非但没有保护，反而在疫苗组里观察到更多的HIV病毒病例，人们陷入了“艾滋病疫苗不会有免疫效果”的失望中。
企业的趋利性使疫苗研发进程再度受挫

　　美泰疫苗给失望者注入了一剂强心剂。但相伴而来的也有坏消息：该项目由美国军方、泰国公共卫生部等机构联合于2003年开始实施，出资人是美国国立研究院。具有讽刺意义的是，虽然“重大成果”“历史性突破”“里程碑”等溢美之词纷纷涌向该疫苗，虽然它可能具有临床使用价值，但疫苗已经用完了！因为在此之前，由于长期看不到效果，生产该联合疫苗的两家欧美公司，一家已停产，另一家则早己倒闭。

　　胡小乐的研究也曾止步于施贵宝公司的经济考虑。上世纪90年代，胡小乐曾与华盛顿大学临床研究学者合作，将该疫苗推进到I期临床试验。但此后他被迫调整研究方向，专门从事以灵长类动物模型为主的应用基础研究。一个重要原因是施贵宝公司决定终止艾滋病疫苗项目，集中力量开发艾滋病药物赚钱。

　　“从经济角度来看，企业的这种做法不失为正确的商业决策，但从科学和社会的角度来说，此举既不科学也不正确。”邵一鸣介绍，目前国际上只有极少数像默克公司这样的巨无霸制药企业，还能开展像艾滋病疫苗这样高风险的项目。因为他们有实力同时投资多个项目，可以用在艾滋病药物和宫颈癌疫苗等项目中赚得的丰厚利润，养着艾滋病疫苗研究。中小药厂则纷纷转入像艾滋病药物这样风险较小、利润很高的研究。艾滋病病人在数十年的治疗过程中，可以不断为药厂送上巨额药费。尽管疫苗是抗击艾滋病最有效的良方，但接种疫苗一劳永逸，不是很好的商业模式。他提出，像艾滋病疫苗这种高风险、高社会效益的药物，是典型的公共产品，必须以政府投资为主导，在科研机构与企业的密切合作下加以推动。

　　呼唤大科学合作

　　美泰疫苗在给艾滋病疫苗带来一线曙光的同时，还极大地震动了以往的设计理念。世界艾滋病疫苗科学正在进行重大调整，整个领域将重新洗牌。

　　“现在对我国艾滋病疫苗研究人员来说，不光是研究方向的重要调整点，还是推进更大规模国内联合合作的契机。”邵一鸣说，艾滋病疫苗这样的世纪性科学难题，百家争鸣和联合攻关同等重要。过去25年艾滋病疫苗研究的重大教训之一是，由大牌科学家为主的主流研究占有了过多的资源和话语权，导致非主流学者的声音被淹没。

　　“艾滋病疫苗的攻坚战，应该是跨学科跨领域的大科学合作，而不是大科学家主导的合作。”在他看来，目前我国艾滋病疫苗研制队伍里，没有一言九鼎的学术权威，这貌似劣势，却是优势。他将此与足球比赛类比：有很多球星的荷兰队赢球不多，反观德国队球星不多，却经常拿冠军。“我们需要这种团体精神。”
几年前，在他的呼吁下，全球艾滋病疫苗联盟建立。今年年初，他与国内学者倡导成立了中国艾滋病疫苗联盟，国内艾滋病疫苗研究的几十家研发单位和企业实现了联合。通过强强联合，协作攻关，形成创新研究。

　　邵一鸣同时建议，我国新药临床试验审批应有所改革，从以往不利于创新性研究的“严进宽出”改成利于创新性研究的“宽进严出”。因为临床研究一直是疫苗和药物研究中最长的阶段，建立鼓励团队研究尽早进入临床研究阶段的新药审评政策，直接关系到我国开展的研究能否在激烈的国际竞争中夺得先机。

　　据邵一鸣介绍，历经10余年的努力，他们已于今年完成了以天坛株痘病毒活载体(中国应用消灭天花的疫苗)为主导的艾滋病疫苗的I期临床研究。

AIDS Vaccine: Non-well-known scientists are ignored
At 07:56 on December 1, 2009 Source: "Science and Technology Daily"
A scientific research for an AIDS vaccine researcher from the endless darkness of the night to see a light: the United States and Thailand, researchers have recently announced that they developed a new type of test human vaccine can reduce the risk of HIV infection 31.2%. This is the discovery of HIV in 1983, the world's first have a certain effect of AIDS vaccine immunization. Despite its immune effect is still very limited, but in the end achieved a leap in the immune effects from scratch.

However, in the just-concluded 2009 World AIDS Vaccine Conference, as is currently the world's only to carry out clinical trials of live vector vaccine researchers, the Chinese Center for Disease Control and Prevention of AIDS Shao Yiming, chief expert, said in a speech the first thing is that we now technical line, as well as the United States and Thailand Vaccine Phase Ⅲ clinical research, are 20 years of Peucedanum Xiaole basis of the work of Professor evolved. Unfortunately, that year, this "non-famous scientist" view is not taken seriously. Otherwise, 10 years ago, we might get today's result.

20 years ago, the non-famous scientist of the research has been neglected

In the Baidu Type "Hu Xiao-le AIDS" entry, in which a search result, in 1993, No. 5 issue of "Biology Bulletin", which records the Chinese-American scientists, HU Xiao-Yue research team at the time: "in macaques successfully tested a vaccine against AIDS. all the subjects in the vaccinated monkeys after the immune system are greatly increased. acceptance of the vaccine is not only their own subjects monkey will not be infected with HIV, and will not become a carrier of the virus ... ... "

In fact, as early as in 1989, Hu Xiao-le presented in the paper may be no effect of the use of two separate vaccines form a "combined vaccine", which the first New York strain of pox virus vectors are responsible for the beginning of live free to carry out attacks on HIV preparation; second vaccine proteins is to act as "assists hand." This "early-free - to strengthen the" line of thinking has been applied in the United States and Thailand vaccine Phase Ⅲ clinical research design. However, Hu Xiao-Le was just the U.S. mid-sized pharmaceutical companies Bristol-Myers Squibb's chief scientist of AIDS vaccine research and its results have not been the industry's attention.

Those who can influence the direction of a great scientist according to the academic theory of scientific thinking, take it for granted that the dead than the living carriers carrier safety better, almost the entire field of AIDS vaccine have been carried out in non-replicating vector-based vaccines and in the death of T cell immunity oriented research.

HU Xiao-Yue study of non-mainstream voices have been drowned. In 1997, Merck & Co. plans to spend huge sums of money to start an AIDS vaccine, when used, is also a non-replicating adenovirus vector vaccine died, however, plan to spend several hundred million dollars in 2007, was discontinued. Clinical trial results showed that the vaccine not only failed to protect, but observed in the vaccine group where the HIV virus to more people caught in the "AIDS vaccine will not have immunity effect" of disappointment.
Benefits or reduce business of making another setback in the process of vaccine development

The vaccine to the United States and Thailand has injected a dose of disappointments tonic. However, there are also often accompanies bad news: The project by the U.S. military, the Thai Ministry of Public Health and other institutions was introduced in 2003, the United States National Institute of investors. Ironically, although "significant results" "historic breakthrough" "milestone" and other words of praise have flocked to the vaccine, although it may have clinical usefulness, but vaccines have been used up! Because Prior to this, can not see because of the long-term effects, the production of the combined vaccine two European and American companies, one has been discontinued, while another has been closed down early.

HU Xiao-Yue's study has also stop at the Bristol-Myers Squibb Company's economic considerations. 90s of the last century, Hu Xiao-Le has worked with the University of Washington Clinical Research Fellow co-operation to promote the vaccine to Phase I clinical trials. But then he was forced to adjust the directions of research dedicated to primate animal model-based applied basic research. One important reason is that Bristol-Myers Squibb Company decided to terminate the HIV Vaccine Project, a focus on developing AIDS drugs to make money.

"From an economic point of view, the enterprise's such an approach may well be the right business decisions, but science and social point of view, this is neither scientific nor correct." SHAO Yiming, at present, only a very few, like Merck & Co. giant companies like pharmaceutical companies, but also to carry out such a high risk such as an AIDS vaccine projects. Because they have the strength to invest multiple items can be used in AIDS drugs and cervical cancer vaccine project earned huge profits, Pan raises AIDS vaccine research. Medium and small pharmaceutical companies that have transferred the risk of AIDS drugs such as smaller, highly profitable research. AIDS patients in the course of treatment for decades, you can continue to send huge pharmaceutical drugs. Although the vaccine is the most effective remedy to fight against AIDS, but the vaccination once and for all, not a very good business model. He proposed that an AIDS vaccine, as this high-risk, high social benefits of the drugs, is a typical public goods, must be led by government investment in scientific research institutions and enterprises in close cooperation to promote it.

Calling large scientific cooperation

Vaccine in the United States and Thailand to bring a ray of hope for an AIDS vaccine, it is also greatly shocked the previous design. World AIDS vaccine science is undergoing major adjustments, the whole area will be re-shuffle.

"Now China's AIDS vaccine researchers, is not only an important research direction to adjust points, or to promote joint cooperation on a larger scale of domestic opportunity." SHAO Yi-ming said that an AIDS vaccine this century scientific challenges, competition and joint research are equally important . AIDS vaccine research over the past 25 years, is one of the major lessons from the big mainstream research scientists, mainly occupy too much resources and the right to speak, leading to non-mainstream voices of scholars, be submerged.

"AIDS Vaccine of critical cross-cutting should be a large interdisciplinary scientific cooperation, rather than a great scientist-led co-operation." In his view, China's current AIDS vaccine development team, there is no authoritative, academic authority, this looks like a disadvantage , it was advantage. He framed it with the football game analogy: There are a lot of players in the Dutch team winning more than the contrary, the German team players much, but I used to get title. "We need this kind of team spirit."
A few years ago, in his appeal, the global AIDS vaccine Union to establish. Earlier this year, he and Chinese scholars advocated the establishment of a Chinese AIDS vaccine Union, the AIDS vaccine research in dozens of R & D units and joint enterprises. By powerful alliances, collaborative research, the formation of innovative research.

SHAO Yiming also proposed clinical trials of new drug approval in China there should be some reform, from the past is not conducive to innovative research, "Yan easy out" conducive to innovative research into the "lenient entry, stringent exit." Because clinical studies of vaccines and drug research has been the longest stage of team building to encourage research into the clinical research stage as soon as possible new drug review policy, is directly related to our ability to carry out research in the fierce international competition won opportunities.

According to Shao Yiming briefing, after more than 10 years of effort, they completed this year to the Temple of Heaven strain of pox virus live vector (China applied the eradication of smallpox vaccine) as the leading AIDS vaccine Phase I clinical study.