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Will China’s scientists’ breakthrough sound death knell for world’s deadly viruses?

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Will China’s scientists’ breakthrough sound death knell for world’s deadly viruses?

Peking University research could help simplify development of effective vaccines or cures for infections such as bird flu, Sars, Ebola and HIV within weeks of an outbreak

Chinese scientists may have found the key to creating effective vaccines for the world’s deadly viruses – by breaking two taboos in traditional vaccinology.

An experiment by a research team at Beijing’s Peking University was hailed as “revolutionary” in the field in a paper published in the latest issue of Sciencemagazine on Friday.

The scientists broke two of the field’s taboos first by creating a vaccine using a live, fully infectious virus, and then by injecting the substance into infected animals dying of the same virus.

The animals were cured after receiving the injection, according to the paper.

This breakthrough promises to simplify the process of producing vaccines, which may help scientists develop effective vaccines or even cures for various viruses – such bird flu, Sars, Ebola and HIV – within weeks of an outbreak.

The live virus used in the vaccine used by the researchers had its genetic code tweaked to disable the viral strains’ self-replication mechanism. But it was kept fully infectious to allow the host animal cells to generate immunity.

Using live viruses in their fully infectious form was considered taboo, as viruses spread rapidly. Vaccines sold and used widely today generally contain either dead or weakened forms of viruses.

Live viruses used in vaccines approved for clinical use have typically had their physical structure altered to weaken them. But this has affected the vaccines’ effectiveness. Vaccines also do not exist for many of the world’s deadly viruses.

Zhou Demin, a professor at Peking University’s School of Pharmaceutical Sciences, and the study’s lead scientist, said researchers had been facing a losing battle against viruses.

“Now we have a new weapon ... that can mow down nearly any kind of virus and their mutations. It can shift the battle,” Zhou told the South China Morning Post.

In the experiment reported in Science magazine, Zhou’s team made the vaccine using live bird flu virus.

They jabbed the vaccine into mice, guinea pigs and ferrets. The virus invaded the hosts and created havoc in cells, but they did not reproduce themselves.

The immune system fought back and picked out the virus in each cell, one after another. By the end of the third day the last strain of the virus was gone, leaving no trace behind except a permanent memory in the host’s immune system, which provided immunity.

The researchers then injected the vaccine into mice suffering from the flu. The animals recovered quickly and returned to full health.

Analysis showed that the man-made virus had recombined with the wild virus so that the combined virus was unable to reproduce, too.

“The vaccine is not just a vaccine, but also a drug,” Zhou said.

The bird flu virus in the vaccine had more than a 99 per cent similarity to its natural cousin.

The researchers tweaked as few as three genome bases in the virus’ DNA. A typical virus has hundreds of thousands of such bases.

A virus needs food and amino acids, the building blocks of proteins found in animals and plants, is one source of food. A wild virus will eat almost any amino acid, but the genetically tweaked virus in Zhou’s vaccine would accept only a special kind of man-made amino acid.

The unnatural amino acid can be produced only in a laboratory: it does not exist in the body of animals or humans.

“So after you inject these viruses into the host they will not be able to reproduce themselves due to the lack of a [suitable] amino acid, and they will ‘starve’ to death in the end,” Zhou said.

Zhou’s team produced the virus in a man-made cell line. The cells were filled with the unnatural amino acid. The virus would then find comfort in these man-made cells and reproduce in large numbers, like cars rolling off a production line.

Zhou has envisioned a likely use for the vaccine technology in the near future, such as a time when a nation is hit by an outbreak of something like severe acute respiratory syndrome.

Researchers would quickly isolate the unknown viral strain from patients and modify three genetic bases in the virus. The modified virus would then be used to vaccinate the general population. All this could be done within a few weeks.

The vaccine could also be injected into patients already suffering from the viral infection.

“The side effect is so small that the recipient would hardly feel anything,” Zhou said.

He said he believed the technology would benefit patients “soon”.

The team had acquired international patents for the technology and they were in contact with some vaccine manufacturers so that trials in humans could be carried out, he said.

In the past, vaccine development has been a long and complicated process, requiring researchers to know exactly the physical structures of a virus and its behaviour.

However, that would not be necessary using the new method, which requires only the modification of a few genetic bases that exist in the DNA of almost any virus.

Professor Meng Songdong, a researcher at the Chinese Academy of Sciences’ Key Laboratory of Pathogenic Microbiology and Immunology, said the work by Zhou’s team was a “new approach” and “something never thought of by others before”.

Meng, who was not involved in the study, added: “It shed a new light on how to deal with the virus.”

However, he raised concerns about whether the live virus vaccine could be used on humans in the near future.

The man-made virus might undergo unexpected mutations that broke the link of control initially created by researchers, he said.

And the recombination of a man-made virus with wild types might not always produce the good results that had been reported by Zhou’s team, Meng added.

“The chances are the exchange of genetic information will make [the virus] even deadlier, even more productive,” Meng said.

“I doubt health authorities in any country, especially China, will vaccinate the public with a live virus.”

http://www.scmp.com/news/china/arti...-breakthrough-sound-death-knell-worlds-deadly
 
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Will China’s scientists’ breakthrough sound death knell for world’s deadly viruses?

Peking University research could help simplify development of effective vaccines or cures for infections such as bird flu, Sars, Ebola and HIV within weeks of an outbreak

Chinese scientists may have found the key to creating effective vaccines for the world’s deadly viruses – by breaking two taboos in traditional vaccinology.

An experiment by a research team at Beijing’s Peking University was hailed as “revolutionary” in the field in a paper published in the latest issue of Sciencemagazine on Friday.

The scientists broke two of the field’s taboos first by creating a vaccine using a live, fully infectious virus, and then by injecting the substance into infected animals dying of the same virus.

The animals were cured after receiving the injection, according to the paper.

This breakthrough promises to simplify the process of producing vaccines, which may help scientists develop effective vaccines or even cures for various viruses – such bird flu, Sars, Ebola and HIV – within weeks of an outbreak.

The live virus used in the vaccine used by the researchers had its genetic code tweaked to disable the viral strains’ self-replication mechanism. But it was kept fully infectious to allow the host animal cells to generate immunity.

Using live viruses in their fully infectious form was considered taboo, as viruses spread rapidly. Vaccines sold and used widely today generally contain either dead or weakened forms of viruses.

Live viruses used in vaccines approved for clinical use have typically had their physical structure altered to weaken them. But this has affected the vaccines’ effectiveness. Vaccines also do not exist for many of the world’s deadly viruses.

Zhou Demin, a professor at Peking University’s School of Pharmaceutical Sciences, and the study’s lead scientist, said researchers had been facing a losing battle against viruses.

“Now we have a new weapon ... that can mow down nearly any kind of virus and their mutations. It can shift the battle,” Zhou told the South China Morning Post.

In theexperiment reported in Science magazine, Zhou’s team made the vaccine using live bird flu virus.

They jabbed the vaccine into mice, guinea pigs and ferrets. The virus invaded the hosts and created havoc in cells, but they did not reproduce themselves.

The immune system fought back and picked out the virus in each cell, one after another. By the end of the third day the last strain of the virus was gone, leaving no trace behind except a permanent memory in the host’s immune system, which provided immunity.

The researchers then injected the vaccine into mice suffering from the flu. The animals recovered quickly and returned to full health.

Analysis showed that the man-made virus had recombined with the wild virus so that the combined virus was unable to reproduce, too.

“The vaccine is not just a vaccine, but also a drug,” Zhou said.

The bird flu virus in the vaccine had more than a 99 per cent similarity to its natural cousin.

The researchers tweaked as few as three genome bases in the virus’ DNA. A typical virus has hundreds of thousands of such bases.

A virus needs food and amino acids, the building blocks of proteins found in animals and plants, is one source of food. A wild virus will eat almost any amino acid, but the genetically tweaked virus in Zhou’s vaccine would accept only a special kind of man-made amino acid.

The unnatural amino acid can be produced only in a laboratory: it does not exist in the body of animals or humans.

“So after you inject these viruses into the host they will not be able to reproduce themselves due to the lack of a [suitable] amino acid, and they will ‘starve’ to death in the end,” Zhou said.

Zhou’s team produced the virus in a man-made cell line. The cells were filled with the unnatural amino acid. The virus would then find comfort in these man-made cells and reproduce in large numbers, like cars rolling off a production line.

Zhou has envisioned a likely use for the vaccine technology in the near future, such as a time when a nation is hit by an outbreak of something like severe acute respiratory syndrome.

Researchers would quickly isolate the unknown viral strain from patients and modify three genetic bases in the virus. The modified virus would then be used to vaccinate the general population. All this could be done within a few weeks.

The vaccine could also be injected into patients already suffering from the viral infection.

“The side effect is so small that the recipient would hardly feel anything,” Zhou said.

He said he believed the technology would benefit patients “soon”.

The team had acquired international patents for the technology and they were in contact with some vaccine manufacturers so that trials in humans could be carried out, he said.

In the past, vaccine development has been a long and complicated process, requiring researchers to know exactly the physical structures of a virus and its behaviour.

However, that would not be necessary using the new method, which requires only the modification of a few genetic bases that exist in the DNA of almost any virus.

Professor Meng Songdong, a researcher at the Chinese Academy of Sciences’ Key Laboratory of Pathogenic Microbiology and Immunology, said the work by Zhou’s team was a “new approach” and “something never thought of by others before”.

Meng, who was not involved in the study, added: “It shed a new light on how to deal with the virus.”

However, he raised concerns about whether the live virus vaccine could be used on humans in the near future.

The man-made virus might undergo unexpected mutations that broke the link of control initially created by researchers, he said.

And the recombination of a man-made virus with wild types might not always produce the good results that had been reported by Zhou’s team, Meng added.

“The chances are the exchange of genetic information will make [the virus] even deadlier, even more productive,” Meng said.

“I doubt health authorities in any country, especially China, will vaccinate the public with a live virus.”

http://www.scmp.com/news/china/arti...-breakthrough-sound-death-knell-worlds-deadly


Good going chaps!!

Credit where credit is due... but you chaps ought to share it with the world at large.
 
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Now this is huge. :tup::tup::tup:

Chinese scientists create flu vaccine from live virus using "revolutionary" approach

Source: Xinhua 2016-12-02 05:34:17

WASHINGTON, Dec. 1 (Xinhua) -- Chinese researchers said Thursday they may have found a simple, convenient and potentially "revolutionary" new approach to create effective vaccines by just genetically tweaking live viruses to make them capable of activating the immune system but unable to replicate in healthy cells.

In a proof-of-principle study, the vaccine they developed against flu proved effective in mice, guinea pigs and ferrets, the researchers reported in the U.S. journal Science.

"We believe our approach will become a general, simple and convenient approach for generation of live virus vaccines adapted to almost any viruses," Professor Deming Zhou of Peking University, who led the study, told Xinhua.

"This will help control pandemics of influenza and other life-threatening RNA viruses."

A major challenge for converting infectious viruses, such as those responsible for influenza, Ebola, Zika and AIDS pandemics, into live vaccines is to render them as avirulent as possible while maintaining their high infectivity to elicit sufficient immunity, Zhou said, noting achieving such a feat would "represent a revolution in vaccinology."

Traditionally, vaccines use either dead or weakened forms of viruses. Those containing weakened viruses retain some degree of ability to replicate and therefore still have toxic effects, he said.

In their study, Zhou and colleagues modified a three-consecutive-base-segment in the genome of influenza A virus, known as premature termination codon (PTC), and found their modified virus -- though still just as potent in terms of activating the immune system -- cannot replicate in regular cells.

The new vaccine was found to offer an antibody response comparable to an existing live-virus vaccine, and a second dose further increased the amounts of antibodies by a factor of six to eight.

Similar beneficial effects were seen when the viral vaccine was tested against several different strains of influenza, and tested in guinea pigs and ferrets.

"Vaccination with such live PTC viruses in animal model via the intranasal route elicited all aspects of immune responses including humoral, mucosal and T cell-mediated immunity against hyper-variable and even antigenically distinct influenza virus strains," said Zhou.

"Furthermore, multiple PTCs-harboring viruses are not only prophylactic but also therapeutic to existing infecting viruses," he noted.

Zhou said his team will continue the research on their whole new flu vaccine and test it in clinical trials as early as possible.

http://news.xinhuanet.com/english/2016-12/02/c_135874404.htm
 
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中国科学家或许已经找到创造有效疫苗对付世界最致命病毒的关键——通过打破传统疫苗学的两种禁忌。

2016-12-3 21:21

据香港《南华早报》网站12月2日报道,最新一期《科学》杂志当日刊登的论文叙述了北京大学一个科研团队开展的实验,这项实验被赞为疫苗领域的“革命”。

报道称,该团队打破疫苗研究领域的两大禁忌:先是用具备完全感染力的活病毒创造一种疫苗,然后把疫苗注入感染这种病毒的濒死动物体内。

论文说,这些动物在接受注射之后都彻底痊愈。

报道称,这项突破有望简化疫苗的研发过程,帮助科学家在疫情爆发几周内就得到有效的疫苗甚至疗法,以对付禽流感、非典、埃博拉和艾滋病等各类病毒。

研究人员调整活病毒的遗传密码,使病毒的自我复制机制失效。但是,他们保留病毒的感染力,从而使宿主细胞生成免疫力。

报道称,使用具有完全感染力的活病毒之前被视为一种禁忌,因为病毒会迅速传播。目前广泛销售和使用的疫苗通常要么含有死病毒,要么含有毒性减弱的活病毒。

获准临床使用的活病毒疫苗通常都经过结构上的处理,使病毒的毒性减弱,但这影响了疫苗的效力。此外,很多致命的病毒都没有相应的疫苗。

这项研究的带头人、北京大学药学院教授周德敏说,此前,研究界与病毒的斗争是一场必败之战。

他对《南华早报》说:“现在我们有了新的武器……几乎能够消灭几乎任何一种病毒及其变体。这可以改变这场战斗。”

《科学》杂志称,周德敏的团队开展了三项实验,用活体禽流感病毒制作疫苗。

他们对小鼠、雪貂和豚鼠使用了这种疫苗,它们都迅速恢复了健康。

分析还显示,这种人造病毒与野生病毒重组,从而使生成的病毒不能自我复制。

周说:“这不仅是一种疫苗,也是一种药物。”

这种疫苗使用的禽流感病毒与天然禽流感病毒有99%以上的相似度。

周的研究团队仅仅调整了病毒DNA的三个碱基——病毒通常有几十万个这种碱基。

病毒需要食物才能存活,而氨基酸就是食物的一个来源。野生病毒几乎任何氨基酸都吃,但周德敏他们培育的遗传改性的病毒却只接受一种特定形式的氨基酸。

这种非天然的氨基酸只能在实验室里制造,动物或人体内都不存在。

周说:“所以,把这些病毒注入宿主体内以后,因为缺少(适合的)氨基酸,它们就无法自我复制,最终会‘饿’死。”

周的团队在人造细胞系里制造这些病毒,细胞里充满了非天然的氨基酸。病毒随后将在这些人造细胞里大量自我复制,就像汽车驶下生产线。

周为这种疫苗技术设想了近期可能的用途,比如全国突然发生严重急性呼吸道综合征疫情。

研究人员可以迅速从患者体内分离出这种未知的病毒,修改病毒的三个碱基,然后用遗传改性的病毒生产疫苗提供给公众。这一切只需几周就可实现。

疫苗还可以注射给已经感染病毒的患者。

周说:“副作用非常小,接种者几乎没有感觉。”

他说,他相信这项技术“很快”就将造福于患者。

@TaiShang @AndrewJin et al :cheers:
 
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Read about it last night,great job by Chinese scientists. Indeed revolutionary.:tup:



Virus engineered to rely on artificial amino acids, used as vaccine

You make the virus in cells with a weird amino acid, then use it as a vaccine.


Flu.png

Flu viruses showing the protein coat that surrounds their genetic material.


Synthetic biology has become a catch-all term for attempts to engineer organisms to do things they normally wouldn't. Efforts so far have ranged from assembling logic circuits inside bacteria to replacing an entire bacterial genome with one synthesized from scratch. So far, however, the field has largely produced some extremely impressive proofs-of-concept. There haven't been a lot of advances with obvious practical uses.


That may be about to change. Researchers have taken a technique that's been used a number of times before—engineering cells to use an artificial amino acid—and applied it to make a flu virus that acts as a vaccine. The vaccine is highly effective and, because it depends on an amino acid our cells don't use, it can't cause infections in us. Best yet, if the vaccine gets into cells with a normal flu virus, it interferes with its ability to generate an infection.


All of our proteins are made with different combinations of the same 20 amino acids. While many additional amino acids exist, those 20 appear to be the standard toolkit that all life shares. There are a few exceptional organisms that use a 21st, but these oddball amino acids are usually close chemical relatives of existing ones.


Revising the genetic code

In recent years, researchers have figured out how to get cells to use some of those additional amino acids, which can be chemically distinct from the existing 20. These artificial amino acids open up the possibility of proteins with some dramatically different chemistry, ones that can catalyze different reactions or interact with chemicals that life normally doesn't deal with. So far, the results have been mostly potential.


A team from Peking University, however, has been working on a different use for artificial amino acids: creating viruses that don't work in normal cells. The idea is to turn these semi-artificial viruses into a vaccine.


The logic here is extremely clever. Many vaccines just contain one or a few proteins from an infectious agent. But these aren't always effective, since they lack the complexity and context of an intact virus or bacteria. The same can be true for a vaccine made from a deactivated virus. The alternative, to use a weakened virus, runs the risk that people with a weak immune system may experience a full infection.


How can artificial amino acids help with this? Well, if you make a virus that depends on them, then it can only reproduce in cells that will provide that amino acid. Since that would exclude all of our cells, using this virus as a vaccine poses no risk of creating an infection. To the immune system, it should look a lot like a normal virus, so it should be an effective vaccine.


Rather than focusing on an artificial amino acid that has a radically different chemistry, the people behind the new work decided to use one that's a close chemical relative to an existing one. And to make things convenient, they picked one that's already used by a microbe. This meant that all the genes needed to put the amino acid into proteins existed; they just had to be pulled out of the microbe and put into cells that a flu virus could infect.


(The artificial amino acid in question is Ne-2-azidoethyloxycarbonyl-L-lysine. It's closely related to the normal amino acid lysine, and chemically look similar to another normal amino acid. Technically, it's not artificial since it's naturally used by some microbes. But it's artificial in human cells, so we'll keep using that term.)


The system is also effective at making sure any genes that use the artificial amino acid won't work without it. The three-base code for the artificial one is UAG. Humans and most other organisms interpret that code as telling the cell to stop making the protein. Thus, any gene with UAG in the middle will be made into a protein normally by cells with the microbial genes, but will be stopped early and produce a severely truncated version in normal cells.


The genes from the microbe were placed into a human kidney cell line. Tests with a fluorescent protein indicated that, as long as it was supplied in the media used to feed these cells, the artificial amino acid would be incorporated into proteins.


Engineering the virus

The system was tested next using a flu virus. A single amino acid code in one of its genes was altered to UAG. When this version of the virus was placed in normal cells, they didn't produce any functional virus, because translation of that gene was terminated early. But when placed in the kidney cells that carried the microbial system, virus was produced normally. The resulting virus could infect other cells, but if those didn't have the microbial system too, the infection stopped there.


That is, for the most part. Mutations occur at a steady rate, and some of these changed the UAG so that it coded for some other amino acid. If that change didn't inactivate the virus, then it could infect normal cells again. The researchers saw precisely this happening: at a low frequency, normally infective viruses emerged during their tests.


The authors went back and tested 21 other different sites that they changed to UAG, targeting any amino acid that looked chemically similar to the artificial one. Some of these disabled the virus entirely; the artificial replacement was close, but not close enough. But seven of the changes produced a viable virus. And several of these could be combined, making the gene very resistant to this sort of evolutionary change. Gradually, they engineered UAGs into genes on every one of the eight different RNA segments that make up the flu virus.


This virus would grow just fine in the kidney cells engineered to carry the microbial system, and the resulting virus could infect other cells. But unless the cells that it infected also carried the microbial system, then the virus stalled there. No mature viruses were ever produced. And because so many different mutations would be needed to return the virus to its original state, the virus remained dependent upon the microbial genes to reproduce.


This was true when they tested it in animals. While a specific amount of normal virus would kill half the mice it was injected into, they found they could inject 100,000 times as much of the engineered virus and there wouldn't be any indication of any health issues. The mice, however, mounted a robust immune response against the virus, one that was broader than the one generated against a normal flu vaccine. The virus also worked as a vaccine in ferrets and guinea pigs.


The authors also tested what happened if cells were infected both with the engineered virus and a normal flu virus. It turned out the engineered version suppressed the infection of the normal one. Remember where we mentioned that the flu virus has a genome made from eight distinct RNA molecules? In cells infected with both viruses, the progeny were a mixture of segments taken from both sources at random. Thus, the vast majority of viruses produced contained at least one engineered segment and couldn't go on to successfully infect normal cells.


A lot of the promise of synthetic biology seems a bit hand-wavy—we can probably do something useful with this at some point. This has included the use of artificial amino acids. Yes, they could potentially expand life's chemistry, but it wasn't clear that doing so would allow us to do things that the normal amino acids couldn't. Still, this is clearly a case where the artificial ones are central to the biotechnology, and the applications are obvious.
 
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China is going to be the forefront of medical biotech in the near future. Cancer cure will be invented by Chinese scientist. Westerners will take the credit as usual.
 
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