创新型艾滋病粘膜疫苗：充满理性的期待

创新型艾滋病粘膜疫苗：充满理性的期待
2009/11/20/09:51 来源：科学时报
艾滋病是威胁人类健康的最重大挑战之一，严重危害着社会进步与经济增长，艾滋病疫苗研发一直都是一个世界性科学难题。

【慧聪制药工业网】今年9月24日，美国和泰国研究人员共同宣布，双方合作开发试验的一种“联合疫苗”可以将人体感染艾滋病病毒的风险降低31.2%。这是人类首次获得具有一些保护效果的艾滋病疫苗。尽管该疫苗还有很多尚待研究和优化之处，但毕竟让走在探索之路上的人们重新振奋了一下。

而一个多月后的清华大学艾滋病综合研究中心实验室里，张林琦教授向记者介绍了他们的研究团队正在研发的创新型艾滋病粘膜疫苗。它，承载着无数的激动与厚望。

“我们的组合是真正的金三角”

中国医学科学院、清华大学的张林琦教授、中国科学院广州生物医药与健康研究院前任院长陈凌教授（特聘）和香港大学李嘉诚医学院艾滋病研究所的陈志伟教授是目前正在进行中的创新型艾滋病粘膜疫苗的主力军。三个人，分别在三个地方，为了一个共同的目标。陈凌接受电话采访时说，“我们是真正的金三角”。

这个“金三角”的成员多年前在美国就已经相识，但在回国后为中国的生物医药研究的共同事业中建立了合作。而在2008年，由中国医学科学院、中国科学院广州生物医药与健康研究院、香港大学、清华大学联合申请的国家“十一五”“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“创新型艾滋病粘膜疫苗的研发”让这三个人更加亲密地“接触”了，从此，“金三角”正式形成。一年多来，在探索研发创新型艾滋病疫苗等方面取得了一项有重要意义的研究结果，在巴黎刚刚结束的2009世界艾滋病疫苗大会上得以报告，并引起关注。

“过去二十多年的历史证明，研究艾滋病疫苗单靠个人的能力是不够的，甚至靠个别国家都是不够的。面对这个世界性的大难题，需要大团队甚至跨国的团队合作。我们三个人的经验有所不同，却能优势互补。”陈凌告诉记者。此前，陈凌在产业界做了多年，并作为美国默克公司研制Ad5疫苗的第一发明人经历了疫苗的整个流程。张林琦和陈志伟在美国是多年的同事和好朋友，在优化我国天坛痘苗病毒载体方面取得了一系列重要成果，陈志伟还作过第一代非粘膜痘苗病毒艾滋病疫苗的研究，为创新型艾滋病粘膜疫苗的研发奠定了坚实的基础。此外，他们在我国云南、新疆、河南、广西等省做过很细致和广泛的流行病学调查和现场研究。这些都为三人默契的合作打下了基础。

“我们的目标是创新型艾滋病粘膜疫苗”

在清华大学艾滋病综合研究中心，张林琦向记者介绍了创新型艾滋病粘膜疫苗这一具有重要意义的研究结果。

“默克疫苗的失败对我们的提示和警示是，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，也不足以降低病毒在体内的复制水平。”张林琦说，“我们的创新疫苗策略是粘膜疫苗。粘膜表面是抵抗艾滋病病毒的第一防线，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。”

张林琦说，利用基础病毒学和免疫学的最新研究成果，通过对粘膜抗原、粘膜载体、粘膜佐剂和免疫策略的设计与优化，研发能够诱导保护性抗艾滋病病毒粘膜免疫应答的“创新型艾滋病粘膜疫苗”，阻断艾滋病通过性传播的渠道是他们的目标。

在这一研究中，张林琦等人发现通过联合使用改良型痘苗病毒天坛株（MVTT）粘膜载体疫苗和5型腺病毒载体疫苗（Ad5）可以有效地控制，甚至是完全预防高致病性SIVmac239病毒对恒河猴的粘膜途径感染。而全国流行病调查数据显示，我国的艾滋病流行趋势已开始从高危人群向普通人群扩散，而这种扩散主要就是通过粘膜途径感染（性接触）。
他们在中国恒河猴中评估了MVTT疫苗粘膜途径初次免疫和Ad5疫苗肌肉注射加强免疫后的免疫原性，结果表明这种策略在试验猴体内诱发了高水平且持续时间很长的细胞免疫应答。

随后，更为重要的攻毒试验表明，联合使用两种异源病毒载体疫苗所诱发的免疫应答，有效地控制了高剂量、高致病、中和抗体阻抗性SIVmac239病毒对恒河猴的直肠粘膜途径的感染或大大降低病毒在体内的复制。

“2011年，我们期望可以如愿”

采访中，陈凌和他的学生孙彩军一再强调艾滋病疫苗研究和团队合作的重要性。“别人攻不下的难题并不意味着中国的科学家们也攻不下。”他说，艾滋病疫苗研究可以说是目前国际上的最高医学难题，中国在这方面的研究已经积蓄了一些力量及队伍。如果能在世界上第一个攻下这个堡垒，其意义比登月或卫星上天还要大，毕竟那只是步人后尘。“希望有关部门能加大这方面的投入，这不仅是对中国，更是中国对全人类的贡献”。

而这一创新型艾滋病粘膜疫苗完全具有中国自主知识产权。采访中记者了解到，张林琦科研团队正在紧锣密鼓地筹备第二批猴子试验，猴子入选已基本完成。

“我们希望年底前能开始疫苗试验，主要是增加试验动物的数量和对照，并优化免疫方案，进一步了解疫苗保护的效果和机制。”香港大学的陈志伟通过邮件告诉记者。

距离上一次采访陈志伟已经时隔近两年，当时是2007年底，正值他将返回香港的前一日。交谈中，他曾告诉记者，自己正在研究的粘膜免疫法是一块硬骨头，但他们正在想办法把这块硬骨头啃下去。

而今，陈志伟的重心是粘膜疫苗研究，以有效的预防HIV性（粘膜）传播。“我国经性（粘膜）传播的感染已是主要的问题，所以预防HIV性（粘膜）传播的粘膜疫苗意义非常重要。”陈志伟说。

目前，“金三角”正在全力以赴，准备在第二批恒河猴体内进行进一步的确认研究。

“一旦证实，我们将立刻开展人体临床研究的准备。那无疑将对阻断和减缓HIV通过粘膜途径感染（性接触）在我国普通人群的流行具有重大的科学意义和社会意义。”张林琦说，近一段时间，他已经推掉了很多会议，平均每天至少12个小时是在实验室度过。进展到这一步的猴子试验是粘膜疫苗最初研究至今耗资最贵的一个阶段，是非常关键的一步，他们进行得很谨慎。没有国家“十一五”科技重大专项的支持，开展这种水平的科学试验，完全不可能。

据张林琦透露，2010年是关键的一年。如果猴子试验进展顺利，试验结果令人满意，2011年将立刻开展临床试验。巧的是，2011年正值清华大学、香港大学百年校庆，也将是广州生物医药与健康研究院获国家中编办正式批准的五周年院庆。

    “我们三人回国，报效祖国之心非常强烈，会全力以赴。2011年开始临床试验，为清华、港大百年校庆献礼，我希望可以如愿。”陈志伟表示。
Innovative HIV mucosal vaccine: full of rational expectations
2009/11/20/09: 51 Source: Science Times
AIDS is a threat to human health, one of the most important challenges, and seriously endanger social progress and economic growth, AIDS vaccine research and development has always been a world-wide scientific problems.

   【Network】 HC pharmaceutical industry this year, September 24, the U.S. and Thai researchers announced that bilateral cooperation development and testing of a "vaccine" can the human body reduce the risk of HIV infection 31.2%. This is the first time human beings have some protective effect of the AIDS vaccine. Although the vaccine there is still plenty of research and optimization of salt, but after all, so go the people in exploring the road to re-excited a bit.

    And more than a month after the Tsinghua University AIDS Research Center laboratory, Professor Zhang Linqi to reporters about their research team is developing innovative HIV mucosal vaccine. It carries many of the excitement and high expectations.

    "Our combination is a real Golden Triangle"

    Chinese Academy of Medical Sciences, Tsinghua University Professor Zhang Linqi, the CAS Guangzhou Institute of Biomedicine and Health Research Institute and former President Professor Chen Ling (Distinguished) and the University of Hong Kong Li Ka Shing Institute of Medicine Professor Chen Zhiwei of AIDS is currently under way in the innovative AIDS the main force of mucosal vaccines. Three individuals, each of the three places, for a common goal. Lynn Chen in a telephone interview, said, "We are truly the Golden Triangle."

    The "Golden Triangle" of the members of many years ago in the United States has been met, but after returning home to China's biomedical research to establish the common cause of cooperation. In 2008, by the Chinese Academy of Medical Sciences, Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health Research Institute, Hong Kong University, Tsinghua University, a joint application of the national "Eleventh Five-Year" "major infectious diseases such as AIDS and viral hepatitis prevention and control" technology major projects " innovative AIDS vaccine research and development mucosa "Let these three individuals more intimately" engagement ", and from the" Golden Triangle "was officially formed. Over the past year to explore innovative AIDS vaccine research and development has made a significant research findings, in Paris, the just-concluded 2009 World AIDS Vaccine Conference to be reported, and cause for concern.

    "In the past 20 years, history has proven that AIDS vaccine research is not enough to rely solely on the ability of individuals, or even by individual countries are not enough. The face of this major world problem, need a big team, and even transnational team. We are three is different from personal experience, able to complement each other. "Ling Chen told reporters. Prior to that, CHEN Ling doing for many years in industry, and as the U.S. Merck's Ad5 vaccine developed the first vaccine inventor has experienced the entire process. In the United States, and Chen Zhiwei Zhang Linqi colleague and good friend for many years, the Temple of Heaven vaccinia virus vector in optimizing China made a series of important results, Chen Zhiwei also made first-generation non-mucosal vaccinia virus AIDS vaccine research, for innovative HIV mucosal vaccine research and development has laid a solid foundation. In addition, they in China, Yunnan, Xinjiang, Henan, Guangxi and other provinces conducted a very detailed and extensive epidemiological surveys and field research. Three of these have laid the foundation for tacit co-operation.

    "Our goal is to innovative mucosal AIDS vaccine"

    AIDS Research Center at Tsinghua University, Zhang Linqi to reporters about the innovative HIV mucosal vaccine that significant research findings.

    "Merck vaccine failure of our tips and alerts is simply to induce T-cell response to vaccine strategies not block the sexual transmission of HIV, but also enough to reduce the level of virus replication in the body." Zhanglin Qi said, "we mucosal vaccine strategy is the innovative vaccines. mucosal surface is the first line of defense against HIV through mucosal immunization strategy targeting in vivo induced by highly active anti-HIV mucosal immune response. "

    Zhang Linqi said that the use of basic virology and immunology of the latest research results, through the mucous membrane antigen, mucous membrane carrier, mucosal adjuvants and immunization strategy design and optimization, R & D can induce protective anti-HIV mucosal immune response of the "innovation-based AIDS mucosal vaccines ", block sexual transmission of AIDS through the channels is their goal.

    In this study, Zhanglinqideng found through the joint use of modified Vaccinia (MVTT) mucosal vaccine vectors and adenovirus type 5 vector vaccine (Ad5) can be effectively controlled, or even completely prevent the highly pathogenic SIVmac239 virus means of infection of the mucous membrane of the rhesus monkey. Compared to the national epidemiological survey data show that trends in China's AIDS epidemic has begun to spread high-risk groups to the general population, which spread mainly through the mucous membrane means infection (sexual contact).
    Rhesus monkeys in their assessment of China's MVTT means the initial mucosal immunization and vaccine Ad5 vaccine after intramuscular injection to enhance the immunogenicity of immunization results show that the trial of this strategy in vivo induced a high level of monkeys and a long duration of cellular immune responses .

    Subsequently, more importantly, to attack drug tests showed that the joint use of two kinds of heterologous virus vector vaccine-induced immune response, effectively controlled the high-dose, high-pathogenic, and in antibody resistance of SIVmac239 virus in rhesus monkeys rectum mucosal route of infection or significantly reduce the replication of the virus in the body.

    "By 2011, we look forward to Ruyuan"

    During the interview, Chen Ling and his student, SUN Cai-jun has repeatedly stressed that AIDS vaccine research and the importance of teamwork. "Other people no less than to attack the problem does not mean that China no less than the scientists were also attacked." He said that AIDS vaccine research can be said that the highest current international medical problems, China's research in this area has already accumulated a number of forces and teams. If the world's first capture of the fortress, its meaning than the bigger the moon or a satellite into space, after all, it is only other people's footsteps. "We hope the relevant departments to step up investment in this area, it is not only for China, but also China's contribution to humanity."

    And this innovative HIV mucosal vaccine entirely with Chinese intellectual property. An interview with reporter has learned that Zhang Linqi research team is in full swing to prepare for the second monkey experiment, the monkeys selected have been basically completed.

    "We hope that vaccine trials will begin before the end of the year, mainly to increase the number of experimental animals and controls, and optimizing the immunization program to better understand the effects and mechanisms of vaccine protection." Zhi-Wei Chen University of Hong Kong told reporters via e-mail.

    Chen Zhiwei from the last interview had been after a lapse of nearly two years, was the end of 2007, a time when he will return to Hong Kong the day before. Conversation, he told reporters that she is studying mucosal immunity law is a hoe, but they are now looking for a way to continue eating this piece of unyielding.

    Today, Chen Zhiwei of the focus is on mucosal vaccine research, with effective prevention of HIV sexual (mucosal) Dissemination. "Our country through sexual (mucosal) dissemination of the infection is a major problem, so prevention of HIV sexual (mucosal) dissemination of the meaning of the mucosal vaccine is very important." Zhiwei said.

    At present, the "Golden Triangle" making every effort in preparation for the second batch of rhesus monkeys in vivo studies for further confirmation.

    "Once confirmed, we will immediately prepare to conduct a human clinical studies. It will undoubtedly block and slow down HIV infection through the mucous membrane channels (sexual contact) in our general population, the prevalence of great scientific significance and social meaning." Zhang Linqi said, Recently, he has turned down a lot of meetings, with an average of at least 12 hours a day is spent in the laboratory. Progress to this step of the monkey trial is the first study of mucosal vaccine has cost the most expensive stage is a very crucial step, they carried out very carefully. There is no national "Eleventh Five-Year" science and technology support to major projects to carry out this level of scientific experiments, impossible.

    According to Zhang Linqi revealed that 2010 was a critical year. If the monkey experiment proceeded smoothly, the results are satisfactory, in 2011, will immediately conduct clinical trials. Coincidentally, in 2011 coincided with Tsinghua University, University of Hong Kong centennial celebration, will also be the Guangzhou Institute of Biomedicine and Health prepared by the Office of the State formally approved a five-Anniversary.

    "The three of us returned home to serve the motherland very strong heart will go all out. In 2011 to begin clinical trials of Tsinghua University, University of Hong Kong centennial celebration gift, I hope to Ru Yuan." Zhiwei said.