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UCLA 孙仁教授团队研制出新的“超干扰素敏感”(HIS)流感毒株
UCLA 孙仁教授团队研制出新的“超干扰素敏感”(HIS)流感毒株
来源:sciencenet | 作者:刘霞 | 1/24/2018 1:51:53 AM | 浏览:730 | 评论:0

UCLA 孙仁教授团队研制出新的“超干扰素敏感”(HIS)流感毒株

A new vaccine based on the influenza virus can soon be used to against a wide range of flu viruses. Photo:Reuters/Eric Gaillard

新疫苗可提高免疫细胞对抗流感能力
距研制出通用流感疫苗更近一步

据《科学美国人》官网近日报道,中美科学家研制出一种新型流感疫苗,可提高免疫系统对抗流感毒株的能力,动物实验显示新疫苗安全有效。研究人员认为,这一成果距最终研制出通用疫苗更近了一步。

迄今没有一种疫苗可以抵御所有流感病毒,因此,研制出通用流感疫苗也成为相关研究人员心中的“圣杯”。为了研制新疫苗,加州大学洛杉矶分校药理学教授孙仁领导的团队分析了流感病毒的整个基因组,并测试了每个部分在接触干扰素(病毒攻击时释放的蛋白质,有助于防止流感)时不同的突变情况,确定了8种最有可能使病毒对干扰素产生保护性对抗的突变,然后将这8种突变合并成一种新的“超干扰素敏感”(HIS)流感毒株。研究人员认为,这种新菌株可能成为更广泛而有效的流感疫苗的基础。

研究人员用几只实验小鼠和雪貂(流行性感冒通用测试模型)对疫苗进行了测试,结果表明,新疫苗不仅安全,而且有效。

他们在发表于最新一期《科学》杂志上的论文中指出,新疫苗可引发强烈的免疫反应,但不会使受感染动物生病。而且,与目前的流感疫苗不同的是,新疫苗还引发了抗病白血球(T细胞)的强烈反应。这一点很重要,因为T细胞反应可能会比目前的接种方法产生更长期的保护作用,并抵御多种流感毒株。

研究人员表示,最新研究可能还有其他应用,如在实验室分离出其他病毒,找出重要突变,并研制出针对大量其他感染的疫苗。

不过,斯克里普斯研究所的科学家在《科学》杂志的评论中表示,尽管这一疫苗可对抗流感病毒株H1N1和H3N2亚型,但不一定能对抗所有流感毒株。此外,触发对病毒的强大免疫反应是否会将人类置于风险之中?这也是个问题,因为疯狂的免疫系统反应会破坏肺组织,甚至导致某些H5N1型禽流感患者死亡。

 

Flu Vaccine Based On Influenza Virus Genome Could Reduce Healthcare Costs

Scientists are trying a new approach to developing vaccines that could lead to the production of a flu vaccine capable of effectively targeting a wide range of flu viruses. This could then be helpful in curtailing hospitalizations and reducing healthcare costs.

The radical approach that UCLA scientists are developing involve identifying and eliminating the defense mechanisms of a virus at the genome level. In their study, which was published in the journal Science, scientists altered influenza virus to stimulate strong immune responses in animals. 

UCLA scientists first focused on identifying the parts of the influenza virus genome responsible for its anti-interferon properties — a process that took four years to realize. After determining the functions of every amino acid in the influenza virus genome, scientists deactivated the sequences that hamper the stimulation of interferons in the immune system. This way, they could ensure that interferon production would be greater when the vaccine is used. 

Interferons are proteins released by cells in response to entry of viruses into body. They are the first line of defense against invading viruses, and they also coordinate the adaptive immune responses that lead to long-term protection against viruses. The latter principle is actually the one that is vital to vaccination, or the administration of antigenic material to produce a lasting protection against a disease. 

The problem, however, is the fact that viruses are smart microorganisms. They have managed to develop their own ways to evade detection of the immune system, thereby limiting the stimulation of much-needed interferons to deal with them. For this very reason, UCLA scientists found the need for developing a new approach to creating vaccines. 

“If viruses do not induce interferons, they will not be killed in the first-line defense; and without interferons, the adaptive immune response is limited,” the study’s senior author Ren Sun, who is a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and of bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science, said. “For these reasons, viruses have evolved strategies to evade detection and limit the production of interferons by host organisms.”

It’s worth mentioning that researchers have been disabling genetic sequences that prevent interferon induction for some time now. Unlike before however, UCLA scientists are disabling multiple interferon-evasion sites on the virus. “Other researchers have knocked out one anti-interferon sequence, but we knocked out eight locations by changing one amino acid at a time,” the study’s first author Yushen Du, who recently earned her doctorate at UCLA, said. 

According to the study, the engineered influenza virus that no longer has interferon-evasion functions generates very strong immune responses. The virus is of course weakened in typical hosts to ensure that it is safe as it is effective. “With this approach, the safety and efficacy requirement of vaccines can potentially be achieved simultaneously. In traditional vaccine development, one is usually sacrificed for the other,” Sun explained.

The new approach has helped UCLA scientists develop a vaccine candidate that could be used against flu viruses. “Because the variations of seasonal influenza viruses can be unpredictable, current vaccines may not provide effective protection against them. Previous pandemics and recent outbreaks of avian influenza highlight the need to develop vaccines that offer broader, more effective protection,” Sun said. 

The vaccine candidate still needs thorough evaluation and it also needs the approval of the FDA before it can be circulated commercially. For now, Sun and his colleagues are focused on testing the vaccine in animals with two strains of influenza. After this, they could move to doing clinical trials with humans. Sun is also encouraging other scientists to try the new approach in creating other vaccines for a wide range of viruses. 

 

The flu vaccine could get a much-needed boost

New approach developed at UCLA could help curtail hospitalizations due to influenza infection

 | 

UCLA 孙仁教授团队研制出新的“超干扰素敏感”(HIS)流感毒株
National Institute on Allergy and Infectious Diseases, NIH

Influenza virus particles. UCLA scientists developed a new technique to identify and eliminate the virus’s defense mechanisms.

More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014–15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help lower that figure for future flu seasons.

The scientists used leading-edge genomics to identify and eliminate the virus’s defense mechanisms, enabling them to develop a vaccine “candidate” — meaning that it must still undergo evaluation and approval by the FDA — that in animals has been proven to be safe and highly effective against influenza.

In the study, which was published in the journal Science, the engineered influenza virus induced strong immune responses in animals. While further research will be needed, the UCLA scientists are hopeful that their approach could lead to a new, more effective vaccine that can be taken as a nasal spray at home, rather than as an injection by a health professional.

UCLA 孙仁教授团队研制出新的“超干扰素敏感”(HIS)流感毒株

“Because the variations of seasonal influenza viruses can be unpredictable, current vaccines may not provide effective protection against them," said Ren Sun, a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and the study’s senior author. “Previous pandemics and recent outbreaks of avian influenza highlight the need to develop vaccines that offer broader, more effective protection.”

The key to the new vaccine is an understanding of the interactions between the virus and interferons, which are proteins that are critical to the body’s immune response. Interferons have two main functions:one is a first line of defense to kill invading viruses very quickly; a second is to coordinate the adaptive immune responses, which provide long-lasting protection against the virus. The latter is the basis of vaccination.

“If viruses do not induce interferons, they will not be killed in the first-line defense; and without interferons, the adaptive immune response is limited,” said Sun, who also is a professor of bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science. “For these reasons, viruses have evolved strategies to evade detection and limit the production of interferons by host organisms.”

Sun and colleagues have spent the past four years searching the influenza virus’s entire genome for its anti-interferon properties. After defining the function of every amino acid in the genome, they deactivated the sequences that prevent interferon induction, which meant that interferon production would be highly stimulated in organisms infected with the virus.

“By disabling these interferon-evasion functions, the engineered virus is weakened in typical hosts,” said Yushen Du, the study’s first author, who recently earned her doctorate at UCLA. “At the same time, however, due to interferon stimulation, the engineered virus generates very strong immune responses.”

Sun added:“With this approach, the safety and efficacy requirement of vaccines can potentially be achieved simultaneously. In traditional vaccine development, one is usually sacrificed for the other.”

Although researchers have disabled genetic sequences that block interferon before, the UCLA scientists were the first to systematically identify and eliminate multiple interferon-evasion sites at single amino acid resolution on the virus.

“Other researchers have knocked out one anti-interferon sequence, but we knocked out eight locations by changing one amino acid at a time,” Du said.

Sun and his colleagues now plan to test the vaccine in animals with two strains of influenza before moving to clinical trials with humans.  He said the approach could also be applied to developing vaccines against a wide range of other viruses.

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