抗艾滋疫苗研发接连失败 抗原性设计或成突破口

抗艾滋疫苗研发接连失败 抗原性设计或成突破口

 
 
 
 
 

抗艾滋疫苗研发接连失败 抗原性设计或成突破口
2009年04月09日18:51来源:医药经济报  
 近年来,由世界各大药研巨头领衔开发的抗艾疫苗研发项目接二连三地宣布失败,尤其是Ad5载体疫苗的临床Ⅱb期试验的失败,给艾滋病疫苗研究领域造成了极大影响。抗艾疫苗的研究迷雾重重,究竟路在何方?未来的发展趋势又将如何?

  此时,中国传出喜人消息,首次启动艾滋病疫苗Ⅱ期临床研究。
 
 
上月21日,SFDA正式批准在广西启动该项目,主要目标是在Ⅰ期临床研究的基础上,进一步评价疫苗的免疫原性,并为能否继续进行评价疫苗效力的临床实验提供依据。在国外一些被寄予厚望的研制项目纷纷受阻或失败的背景下,中国艾滋病疫苗Ⅱ期临床研究为什么会选择迎难而上?抗艾疫苗研发再次成为了业界关注的焦点。

  现状 技术难点尚未克服

  近日,记者从卫生部官方网站上获悉,截至2008年9月底,全国前三季度累计报告艾滋病病毒感染者264302例,其中艾滋病病人44839例,报告死亡34864例,死亡率高达13.2%。有专家甚至认为,今年艾滋病病毒已首次成为中国头号传染病杀手,如不采取有效措施,到2010年被感染者累计可能达到1000万。

  无情的数据对艾滋病疫苗研究提出了迫切的要求。事实上,从1981年发现首例艾滋病患者至今,各国对艾滋病药物和疫苗的研究从没间断过,可结果均不尽人意。曾被最为看好的默克细胞免疫候选疫苗试验的失败,再次引发了研发思路的新探索。

  在过去20多年中,科学家们一直都在探索。中国首个抗艾疫苗研究项目负责人、吉林大学生物科学院疫苗研究中心主任孔维教授在接受《医药经济报》记者采访时表示,艾滋病疫苗的发展大致可分为三个阶段:第一阶段主要是以单一组膜蛋白为主,以诱导中和抗体为目标;第二阶段是从依靠中和抗体阻断病毒感染转向借助细胞免疫杀伤被病毒感染的细胞,采用两种或以上疫苗按初免/加强的方式联合免疫;第三阶段是探索诱导出较平衡的体液和细胞免疫反应。

  “事实上,这些年艾滋病疫苗的研发并没有取得突破性的进展,主要原因还是几个技术难点没有克服。”清华大学艾滋病综合研究中心常务副主任张林琦教授向本报记者坦承。这里所说的技术难点是指HIV病毒的高度变异性和在相同或不同个体之间的差异性和多样性,同时也缺乏疫苗研发的理想的动物模型。

  重点 聚焦抗原性设计

  记者通过对全球已进入临床试验的10多种艾滋病疫苗研究进行对比,发现以往国际上的HIV疫苗研究,主要以非复制型病毒为疫苗载体和以诱导细胞反应及降低病毒载量为目标,而当HIV疫苗研制失败后,又过早地放弃了常规疫苗所必要的中和抗体的技术路线而转向细胞疫苗。另外,为了追求绝对安全,放弃了复制性疫苗载体。

  中国究竟会走什么路线?业界一直在争论。记者辗转多时,终于采访到了孔维教授。孔维认为,之前国际上流行的研究领域太过于狭窄,其实思路应该更宽阔一些。“尽管我国也采用了DNA疫苗和病毒载体疫苗联合免疫的方法,诱导人体对艾滋病毒产生特异性细胞免疫反应,但特色之处在于采用了在中国流行比较广泛的流行株,这是专为中国艾滋病患者量身设计的抗艾疫苗。”

  孔维向记者解释道,通过多年的努力,我国逐渐从实验室研究走向产学研相结合的道路并进展到Ⅱ期临床研究,与国外最大的区别就是不走以死疫苗和非复制死载体的研发道路,而坚持以我国独创的慢病毒疫苗EIAV为模型对HIV抗原进行定向改造,这种疫苗研究的关键点就在抗原性设计上。

  对此,有关专家认为,目前用DNA疫苗进行初次免疫,然后用病毒载体疫苗进行增强疫苗,实质上就是要获得理想的广谱保护疫苗,进而刺激抗原的免疫力。当前,艾滋病疫苗广谱交叉技术或成为新热点。

  除了技术因素外,社会环境因素对于研发艾滋病疫苗影响巨大。“政策环境的支持,临床观察的管理、伦理道德的遵循、预防治疗的质量、公众参与的意识等,都直接影响抗艾疫苗研发的进程。”张林琦亦指出,刚宣布成立的中国艾滋病疫苗联盟,就是要发挥中国团队的整体力量展开创新性研究。

  趋势 回归基础研究

  目前各国的艾滋病疫苗临床试验纷纷受阻,必然会造成其研发方向的逐渐集中。据了解,采用DNA疫苗和病毒载体疫苗联合免疫,诱导人体对艾滋病毒产生特异性细胞免疫反应的方法,逐渐成为了未来抗艾药研的主要趋势,目前我国已处于该潮流的前沿。

  在谈到未来艾滋病疫苗研究的趋势时,孔维反复地提醒记者,我国艾滋病疫苗研究在加强临床研究的同时,一定要更加注重基础研究,这一点在国内非常必要也非常必需。“我们应该从国外的惨痛教训中吸取经验,及时调整策略和研究方法,尽量少走弯路。今后,艾滋病疫苗的发展方向应该是继续寻找更强的细胞免疫反应,回到基础研究中去找出减少病毒压制抗体的方式,并将基础免疫病理学的知识用于疫苗发展。”

  那么,怎样才能平衡基础研究和临床研究,大胆的进行创新性研究呢?孔维和张林琦两位教授一致认为,国内外研究试验表明,艾滋病疫苗研究迫切需要根据艾滋病病毒生命周期的关键环节,继续寻找并发现抗艾滋病病毒药物新“靶点”,坚持基础研究与临床研究并重,互为补充。

  从长远来看,只有在基础研究有更大的进步后才能刺激制药公司加强研发艾滋病疫苗的信心。专家认为,目前,国内涉及抗艾研发的制药企业一般是从艾滋病原料药的生产开始,逐渐延伸到制剂的开发,资金和技术缺乏是最现实的问题,而很多企业却把仅有的资金用来研制和测试新的产品,对基础研究则显得太吝啬,这是需要重新思考的问题。 (责任编辑:孙孟)

Series of anti-HIV vaccine research and development of design or failure of antigen into a breakthrough
At 18:51 on April 9, 2009 Source: Medicine Economic News
In recent years, research by the world's major drug giant led the development of anti-AIDS vaccine research and development projects, announced the failure of one after another, especially in the Ad5 vector vaccine clinical trial phase Ⅱ b the failure of AIDS vaccine research field to cause a great impact. Anti-AIDS vaccine research迷雾重重, what go? The development trend of the future, how are they going?

At this time, China reported encouraging news, for the first time to start Phase Ⅱ clinical trial of AIDS vaccine research.
 
 
Last month on the 21st, SFDA formally approved the start of the project in Guangxi, the main goal is to phase Ⅰ clinical research, based on further evaluation of vaccine immunogenicity and ability to continue to evaluate the effectiveness of the vaccine to provide the basis of clinical trials. In some foreign countries have great expectations of the research project delay or failure of their background, China's AIDS vaccine Phase Ⅱ clinical trial of difficulties Why did you choose? Anti-AIDS vaccine research and development of the industry once again become the focus of attention.

Technical problems that have not yet overcome the status quo

Recently, reporters from the official website of the Ministry of Health was informed that as at the end of September 2008, the National AIDS report the first three quarters of a total of 264,302 cases of HIV, including 44,839 cases of AIDS patients, reports 34,864 cases of death, the mortality rate as high as 13.2%. Some experts even believe that HIV has been the first time this year to become the number one infectious disease killer in China if it does not take effective measures to be infected in 2010 may reach 10 million cumulative.

Relentless AIDS vaccine research data has an urgent requirement. In fact, since 1981 has found the first case of AIDS, the AIDS drugs and vaccine research has never stopped to unsatisfactory results. Merck has been the most promising candidates for cell-mediated immunity of the failure of vaccine trials, once again led to the development of new ideas to explore.

In the past 20 years, scientists have been exploring. China's first anti-AIDS vaccine research project, and Jilin University Vaccine Research Center of Biological Sciences Director Professor Kong Wei in an "economic medicine reported that" an interview with reporters that the development of an AIDS vaccine can be broadly divided into three phases: the first phase of the main is based on a single membrane protein-based group to induce neutralizing antibody for the target; the second phase is dependent on neutralizing antibody to block infection with cell-mediated immunity towards anti-virus infected cells, using two or more vaccine-free by the beginning of / the way to strengthen combined immunodeficiency; The third stage is to explore a more balanced induced humoral and cellular immune response.

"In fact, all these years of AIDS vaccine research and development has not achieved a breakthrough in the progress was mainly due to several technical problems still have not overcome." Comprehensive AIDS Research Center of Tsinghua University and executive deputy director of Professor Zhang Linqi admitted to our reporter. Technical difficulties are talking about here is the HIV virus and a high degree of variability in the same or the differences between different individuals and diversity, but also the absence of a vaccine research and development of an ideal animal model.

Key focus of the design of antigen

Through the global clinical trials has more than 10 kinds of AIDS vaccine research are compared and found that previous international HIV vaccine research, mainly in non-replicating virus vectors for vaccine and to induce cell responses and lower viral load as the goal, and When after the failure of HIV vaccine development, but also premature to abandon conventional vaccines and antibodies necessary for the technical route and turn to cell vaccine. In addition, to the pursuit of absolute security and give up the copy of the vaccine vector.

Whether China will take, what route? The industry has been controversial. No news for a long time, and finally to an interview with Professor Kong Wei. KONG Wei believes that the international community before the popular area of research is too narrow, in fact, some thought should be more broad. "Although China has adopted the DNA vaccines and viral vector vaccine approach combined immunodeficiency, induced by the human body to produce HIV-specific cellular immune response, but the feature is that the use of a relatively popular in China a wide range of epidemic strains, which is designed to China tailor the design of AIDS vaccines against AIDS. "

KONG Wei explained to reporters, through years of efforts, China's gradual move from the laboratory study of the combination of research and progress on the road to Phase Ⅱ clinical research, with the largest difference between foreign countries is not going to die the death of vaccines and non-replicating vector R & D road, and adhere to my original lentivirus EIAV vaccine for HIV antigens as a model for targeted transformation, the study of this vaccine on the key points of the design of antigen.

In this regard, the experts believe that the initial use of DNA vaccines for immunization, and then to enhance the vaccine vector vaccines, in essence, is to achieve an ideal broad-spectrum protection of vaccine antigens to stimulate immunity. At present, broad-spectrum cross-AIDS vaccine technology or a new hot spot.

In addition to the technical factors, social environmental factors in the tremendous impact of AIDS vaccine research and development. "The policy environment to support the clinical observation of management, ethics compliance, prevention and treatment quality, a sense of public participation, have a direct impact on anti-AIDS vaccine research and development process."张林琦also pointed out that China has just announced the establishment of the League of AIDS Vaccine is to play the overall strength of the Chinese team carried out innovative research.

The trend of regression of basic research

At present, countries in AIDS vaccine clinical trials have blocked, will definitely lead to the progressive direction of its R & D focus. It is understood that the use of DNA vaccines and viral vector vaccine combined immunodeficiency, induced by the human body to produce HIV-specific cell-mediated immune response approach抗艾药gradually become the next major trends in research, at present China has at the forefront of the trend.

When talking about future trends in AIDS vaccine research, the KONG Wei repeatedly reminded reporters that China's AIDS vaccine research to strengthen clinical research at the same time, we must pay more attention to basic research, it is necessary at home is also very necessary. "We should be learned from abroad in the painful lessons, timely adjustment of strategies and research methods, as little as possible detours. From now on, the direction of development of an AIDS vaccine should continue to look for a stronger cellular immune response and return to basic research to identify the antibody reduced the virus to suppress the way, based on immunopathology and knowledge development for the vaccine. "

[1] [2]  下一页

 
 
 
 
 

[ 作者:佚名    转贴自:本站原创    点击数:196    更新时间:2009-4-10    文章录入:nnb ]

 

 http://www.zyynb.com/admin/Article_Show.asp?ArticleID=5656

 

个人简介
协和专家门诊部艾滋病治疗中心主任、教授、专家,中医药疑难病专治网站长等。论文《艾滋病中医论治探析》登载《中国性病艾滋病》2003版杂志,发明的艾滋病治疗新药康生丹自2002年临床应用至今疗效显著,现有中国唯一艾滋病新药3代…
每日关注 更多
赞助商广告