流感难缠 技术帮忙

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研究者正在开发可以迅速培养并且能对付多种流感病毒株的疫苗。

为什么重要

现在的季节性流感疫苗并不总是有效，而且每年都需要新的疫苗。

每年从9月开始，美国的卫生官员就开始催促你去注射季节性流感疫苗，但即使你注射了疫苗，也不能保证你不得病。

为什么这种常见的疾病如此难以预防，什么技术能改变这样年复一年的挣扎呢？

季节性流感是由流感病毒引起的，这种病毒在人与人之间传播时会发生变异，意味着每年都会出现新的病毒株。你的身体在患病后或对流感病毒疫苗应答产生的抗体在一年后也就无效了。

此外，每个流感季占据优势的都是几种不同的流感病毒株，而卫生官员必须尽力预测要对付的是哪些，因为生产疫苗要用几个月的时间。每年2月，世界卫生组织都会对北半球下一个流感季的疫苗应该包括哪三种病毒提出建议（WHO会在每年9月为南半球提出类似的建议），在美国，食品和药物管理局（FDA）一般会建议把这三种病毒株包含在即将到来的流感季的疫苗中。虽然这方法存在疫苗与下一个流感季中流行的病毒株不匹配的风险，却是必要的。

一种制造流感疫苗的新方法可以缩短漫长的时间线，并且有潜力对意料之外的爆发做出反应。现在，流感疫苗生产始于鸡蛋。活病毒被注入鸡蛋中，在这里病毒进行复制。制造商然后打开鸡蛋，收获并提纯病毒，再杀死病原体并把它们粉碎成更小的片段。来自三种选出的病毒株的灭活片段被混合在一起制成流感疫苗，这些疫苗可以训练身体的免疫系统使其能对真正的病毒产生应答。

来年的疫苗生产可能是不同的，一些制造商可能用一种新方法替代这种耗时的工艺流程。在11月，FDA批准了Novartisde的一种新疫苗，这种疫苗是用人工培养的狗肾脏细胞生产的。在这个月的早些时候，FDA还批准了ProteinsSciences用培养昆虫细胞制造的一种疫苗。FDA的发言人说，这些方法“为比传统基于鸡蛋的疫苗制造办法启动更快速的制造方法提供了潜在的可能。”除此之外，它们也可以帮助对鸡蛋过敏的人安全地接受流感疫苗注射。

公共和私营的研究人员也在努力开发所谓的通用流感疫苗，有了这种疫苗就无需每年注射新疫苗了。当你注射流感疫苗或者说典型的流感疫苗时，你的身体会做出应答，制造与病毒上一种叫做血球凝集素的蛋白质结合的抗体。这种蛋白质让病毒进入细胞，而针对它的抗体可以阻止病毒进入。然而，这种蛋白质变异也非常快，所以你身体今年产生的抗体到明年可能就不认识这种蛋白质了。

伊恩·威尔逊（Ian Wilson）在加利福尼亚州拉荷亚的斯克里普斯研究所（Scripps Research Institute）的研究组，研究了某些人体内产生的可与病毒其他部分结合的稀有抗体。因为它们结合的是变化得不像典型目标那样迅速的蛋白质的区域，这些抗体有希望识别不同种类的病毒株。在最近几年中，不同的研究组表明这样的抗体可以识别多种病毒株，而威尔逊的研究组和库塞尔疫苗研究所（Crucell Vaccine Institute）在2012年9月表明一种抗体可以识别季节性流感各个主要亚型的病毒株，比之前研究展示的抗体识别得更多。

“人们一直在谈论通用疫苗，但直到最近都没有迹象显示这大有希望，”威尔逊说。“但现在，那样可以获得所需类型的免疫应答已得到了证明，”他说。

现在的挑战是开发一种可以引发这种强力而有效的应答的疫苗，并找出一种方法来测试它。“这些更通用的抗体很多都不能用测试抗体效力的标准方法进行检验，”威尔逊说。这意味着制造商和FDA这样的监管部门需要开发新的检验系统。“即使我们现在手中有了完美的疫苗，我们也没有一个获得了批准的合适方法来测试它，“威尔逊说。

宾夕法尼亚州的生物技术公司Inovio正采取一种不同的方法来开发通用疫苗。不同于为人注射灭活的病毒片段或蛋白质，这家公司正在开发一种基于DNA的疫苗。为了让它防护多种病毒株，这家公司把现有病毒株的DNA序列组合到一起成为一支疫苗。结合该公司的专利给药系统，DN***段通过一次注射进入体内。看起来类似钢笔的手持设备能施加微弱的电场，暂时开启细胞膜让DNA疫苗进入细胞，Inovio的CEO约瑟夫•金（Joseph Kim）说。一旦进入细胞，细胞本身的装置会读取DNA并制造出病毒的蛋白质，这些蛋白质就会激活身体的免疫系统。 结果就会让人体制造出针对多种病毒株的抗体。

该公司目前正在65岁或更老的人中测试这种疫苗，与现有流感疫苗一起联合施用。老年人最易受流感侵害并且现有免疫方法对他们的保护也最差。每年大约35000人死于流感，而“90%的死亡患者年龄都在65岁以上，”金说。“但是季节性流感疫苗只能保护大概10%到20%的老人。”

Inovio的临床试验显示把季节性流感疫苗与公司的实验通用疫苗结合起来可以让获得抵抗流感保护的老人数量增加一倍。

“未来难以预测，但如果我们有一种可以防护所有已知优势病毒株的通用疫苗，防护未来的未知病毒的可能性就更高。”金说。“如果我们正确的话，我们可以改变流感免疫的模式，像对待其他免疫接种那样对待它。

星梦78

Why the Flu Is So Relentless, and How Technology Might Help

Researchers are developing quick-brew vaccines and ones that catch multiple strains of flu.


By Susan Young on January 28, 2013

Why It Matters

Current seasonal flu vaccines are not always effective, and new ones are needed every year.

Every year, starting in September, public health officials in the U.S. start prodding you to get this year’s flu shot. But even if you do get one, it is not a guarantee against getting sick.

Why is the common illness so difficult to prevent, and what technologies might change this yearly struggle?  


Seasonal flu is caused by influenza viruses, which can mutate as they spread from person to person, meaning every year brings a new strain of virus. Any antibodies your body produced after getting sick or in response to a flu shot may not work a year later.

Furthermore, each flu season is dominated by several different strains of the virus, and health officials must try to predict which ones to combat because it takes months to produce the vaccine. Every February, the World Health Organization recommends which three viruses should be included in the next season’s vaccines for the Northern Hemisphere (the WHO makes a similar recommendation for the Southern Hemisphere each September), and in the U.S., the Food and Drug Administration typically recommends that those three strains be included in the coming season’s vaccine. While this process carries the risk that the vaccine will not match the dominant strains in the next season, it is necessary.

A new way of making flu vaccines could reduce this long timeline and make it possible to react to unexpected outbreaks. Currently, flu vaccine production starts with chicken eggs. A live virus is injected into eggs, where it replicates. Manufacturers then crack open the eggs, harvest and purify the viruses, and kill the pathogens and chop them into smaller pieces. The inactivated pieces from the three chosen strains are then mixed into a flu vaccine, which trains the body’s immune system to respond to the actual virus.

Next year’s vaccine production could be different, as some manufacturers may replace this time-consuming process with a new approach. In November, the FDA approved a new vaccine from Novartis, which is produced in cultured dog kidney cells. And earlier this month, the agency approved a vaccine made by ProteinsSciences in cultured insect cells. The methods “offer the potential for faster start-up of the manufacturing process than traditional egg-based vaccine methods,” says a spokesperson for the FDA. Additionally, they may help people with egg allergies safely get flu vaccines.

Public and private researchers are also working to develop so-called universal flu vaccines that would preclude the need to get a new vaccine every year. When you get the flu or a typical flu shot, your body responds by making antibodies that glom onto a protein in the virus called hemagglutinin. This protein allows the virus to enter cells, and antibodies against it will prevent that entry. However, this protein also mutates quickly, so that the antibodies your body produces this year may not recognize the protein next year.

Ian Wilson’s group at the Scripps Research Institute in La Jolla, California, has been studying the rare antibodies produced in some people that bind to other parts of the virus. Because they bind to regions of the protein that do not change as quickly as the typical targets, the hope is that these antibodies will be able to recognize many different strains of the virus. Over the last few years, different research groups have shown that such antibodies can recognize multiple flu strains, and a study from Wilson’s group and the Crucell Vaccine Institute in September 2012 showed that one antibody can recognize strains from both major subtypes of seasonal influenza, more than had been previously shown.

“A universal vaccine was something that people always talked about, but until recently, there was no evidence for much hope of that,” says Wilson. “But now, it has been demonstrated that gives the desired type of immune response,” he says.   

The challenge now is to develop a vaccine that will elicit such a powerful and effective response and to find a way to test it. “A lot of these more universal antibodies don’t work in the standard tests for antibody efficacy,” says Wilson. This means that manufacturers and regulators like the FDA will have to develop new assay systems. “Even if we had the perfect vaccine in hand today, we wouldn’t have a good and approved way to test it,” says Wilson.

Pennsylvania-based biotech Inovio is taking a different approach to developing a universal vaccine. Instead of inoculating people with an inactivated virus fragment or protein, the company is developing a DNA-based vaccine. To make it protective against multiple flu strains, the company combines DNA sequences from existing virus strains into a single dose. The DNA pieces are delivered by a shot combined with the company’s proprietary delivery system. A handheld device that looks like a pen delivers a small electric field which temporarily opens up cell membranes to allow the DNA vaccine to enter cells, says Inovio CEO Joseph Kim. Once inside cells, the DNA is read by the cell’s own machinery to build viral proteins which will activate the body’ immune system. The result is that the body creates antibodies against a diversity of flu strains.

The company is currently testing the vaccine in people 65 and older as a combination treatment along with existing flu vaccines. The elderly are the most at risk when it comes to flu and are the least protected by current immunizations. Every year, some 35,000 people die because of the flu and “90 percent of the deaths are in people who are 65 and older,” says Kim. “But the seasonal flu vaccine only protects about 10 to 20 percent of the elderly.”

Inovio’s clinical trial has shown that combining the seasonal flu vaccine with the company’s experimental universal vaccine has doubled the number of elderly protected from the flu.   

“It is hard to predict the future, but if we can have a universal vaccine that can protect against all known dominant strains, the likelihood of protecting against future unknown is much higher,” says Kim. “If we are correct, we can change the flu paradigm into one more like what we do with other vaccinations.”

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Susan Young Biomedicine Editor

I’m the biomedicine editor for MIT Technology Review. I look for stories where technology stands to improve human health or advance our understanding of the human condition.

I joined MIT Technology Review in March 2012 after a brief stint in the Washington, D.C., new

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很好的资料，下载学习，对指导我们搞预防接种起到了重要作用。

孟6386

0002 发表于 2013-1-30 10:09

                               
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很好的资料，下载学习，对指导我们搞预防接种起到了重要作用。

需要人翻译了，不好意思。