万能流感疫苗正向我们走近

Universal Flu Vaccine Moving Closer
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ScienceDaily (July 18, 2010) — A universal influenza vaccine -- so-called because it could potentially provide protection from all flu strains for decades -- may become a reality because of research led by scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Colorized transmission electron micograph (TEM) of influenza A viruses. (Credit: CDC)

% v. R+ J- l% w! T) SIn experiments with mice, ferrets and monkeys, the investigators used a two-step immunization approach to elicit infection-fighting antibodies that attacked a diverse array of influenza virus strains. Current flu vaccines do not generate such broadly neutralizing antibodies, so they must be re-formulated annually to match the predominant virus strains circulating each year.
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The research, led by NIAID scientist Gary J. Nabel, M.D., Ph.D., appears online ahead of print July 15 issue of Science Express.

"Generating broadly neutralizing antibodies to multiple strains of influenza in animals through vaccination is an important milestone in the quest for a universal influenza vaccine," says NIAID Director Anthony S. Fauci, M.D. "This significant advance lays the groundwork for the development of a vaccine to provide long-lasting protection against any strain of influenza. A durable and effective universal influenza vaccine would have enormous ramifications for the control of influenza, a disease that claims an estimated 250,000 to 500,000 lives annually, including an average of 36,000 in the United States."

In parallel experiments with mice, ferrets and monkeys, Dr. Nabel and his colleagues first primed the animals' immune systems with a vaccine made from DNA encoding the influenza virus hemagglutinin (HA) surface protein. After being primed with DNA vaccine, the mice and ferrets received a booster dose of the 2006-2007 seasonal influenza vaccine or a vaccine made from a weakened cold virus (an adenovirus) containing HA flu protein. Monkeys were boosted with the seasonal flu vaccine only.
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This prime-boost vaccine stimulated an immune response to the stem of the lollipop-shaped hemagglutinin of influenza virus. Unlike HA's head -- which mutates readily, allowing the virus to become unrecognizable to antibodies -- the stem varies relatively little from strain to strain. In principle, Dr. Nabel explains, antibodies generated against the stem of HA should be able to recognize and neutralize multiple flu strains.
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Although the DNA in the priming vaccine was derived from a 1999 circulating flu virus, all the animals made antibodies capable of neutralizing virus strains from several other years. Mice and ferrets produced antibodies not only against virus strains dating from before 1999, including a strain that emerged in 1934, but also against strains that emerged in 2006 and 2007.
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" v( T7 d/ p/ K. V0 k) RMoreover, although the prime-boost vaccines were both made from H1 subtypes of influenza A virus, the antibodies they generated neutralized other influenza subtypes, including H5N1 (avian influenza) virus. This indicates that a prime-boost strategy potentially could confer immunity to many or all subtypes of influenza A, says Dr. Nabel.

In another set of experiments, the scientists measured how well the prime-boost vaccine protected mice and ferrets from infection with deadly levels of flu virus. Three weeks after receiving the boost, 20 mice were exposed to high levels of 1934 flu virus, and 80 percent survived. Mice receiving DNA only, seasonal flu vaccine only or a sham prime-boost vaccine all died.
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The researchers saw similar results when they tested several prime-boost combinations in ferrets, which are considered a good animal model for predicting flu vaccine efficacy in humans. All four ferrets that received a DNA prime-seasonal boost were protected from infection with a 2007 virus strain, while all six ferrets that received the DNA prime-cold virus boost combination were protected from the 1934 influenza virus.

* N) F  ]$ |4 o5 z* h7 d/ d4 a& r" dCollaborators on these studies included Terrence Tumpey, Ph.D., of the Centers for Disease Control and Prevention.

* D( c1 f- h( @9 Z9 e/ j8 z# A"We are excited by these results," says Dr. Nabel. "The prime-boost approach opens a new door to vaccinations for influenza that would be similar to vaccination against such diseases as hepatitis, where we vaccinate early in life and then boost immunity through occasional, additional inoculations in adulthood."
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Trials of prime-boost influenza vaccines assessing safety and ability of the vaccine to generate immune responses are already under way in humans, Dr. Nabel adds. The information from the new research will be valuable in selecting candidates to move forward into large-scale trials, he says. "We may be able to begin efficacy trials of a broadly protective flu vaccine in three to five years."

http://www.sciencedaily.com/releases/2010/07/100716125837.htm

万能流感疫苗正向我们走近
# R5 C1 Y2 j: w( v; W+ l《每日科学》2010年7月18日报道 —— 一项由美国国家过敏和传染病研究所（NIAID，隶属国家卫生研究院）的科学家率队进行的研究可能让一种万能流感疫苗 （如此称谓是因为该疫苗可以连续几十年保护疫苗接种者免受流感病毒毒株的感染）成为现实。
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' k3 [+ |9 j+ w: ~6 f4 }透射电子显微镜（TEM）下的甲型流感病毒彩色图像（图片来源：CDC）
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. f6 f( w' k2 a在小鼠、白鼬与猴实验中，研究者采用“两步走”免疫方法来诱导有攻击多种多样形形色色流感病毒毒株能力的抗感染抗体。目前的流感疫苗并不能产生这种具有广泛中和能力的抗体，因此它们必须每年重制以适应每年流行的主导病毒毒株。
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3 p+ j% H0 M/ J3 }: E本研究由NIAID科学家、医学博士、哲学博士Gary J. Nabel率队进行，其成果已先于7月15号的《科学快讯》印刷版而在线发表。

NIAID院长、医学博士 Anthony S. Fauci说：“通过接种产生具有广泛中和能力的抗体来应对多种动物流感毒株是探求万能流感疫苗征程上的一个重要里程碑。这一重大的进步为开发一种能长期保护动物免受所有流感毒株感染的疫苗奠定了基础。一种持久有效的万能疫苗将在流感控制上产生巨大的影响。流感每年夺去250,000到500,000人的生命，其中包括美国的3万6千人（平均）。
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在小鼠、白鼬与猴子的平行实验中，Nabel博士及其同事首先用一种由编码流感病毒血凝素（HA）表面蛋白制出的DNA疫苗使动物的免疫系统准备就绪。在用DNA疫苗准备就绪后，小鼠与白鼬接受2006-2007季节性流感疫苗或由包含HA流感蛋白的弱化感冒病毒（一种腺病毒）制出的疫苗的加强剂量。而猴子则仅接受季节性流感疫苗来加强。
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该“就绪-加强”疫苗刺激了针对流感病毒棒糖形血凝素（HA）主干的免疫响应。与随时会发生变异的（从而允许该病毒变成抗体难以识别的）HA头部不同，每种毒株HA主干相对变化较小。Nabel博士解释说，所产生的抗击HA主干的抗体原则上应该能够识别并中和多种流感病毒毒株。

- p& Y5 M, B% p* I3 ^' S) B虽然“就绪”疫苗中DNA取之1999年流行的流感病毒，所有动物都产生能够中和其它几年里出现的各种各样的病毒毒株的抗体。小鼠与白鼬所产生的抗体，不仅能够对抗1999年以前的病毒毒株（包括1934年出现的一种毒株），也能够对抗2006与2007年出现的各种毒株。

0 S2 l, p1 a( g3 i, F/ c* `. S: ]Nabel博士指出：更进一步的是，虽然就绪-加强疫苗两者都从甲型流感病毒H1亚型制出，它们所产生的抗体则中和了其它流感亚型，包括H5NA（鸟流感）病毒。这指明：“就绪-加强”策略具有为许多或全部甲型流感的亚型提供免疫的潜在能力。

! H% ~1 J2 ~: F4 R- x# c在其它一组实验中，科学家测量了该就绪-加强疫苗保护小鼠与白鼬免受致命水平的流感病毒感染的程度。接受加强剂量疫苗后三周，20只小鼠被注射高水平1934流感病毒，80%的小鼠存活了下来。仅接受DNA、仅接受季节性流感疫苗或接受假的就绪-加强疫苗的小鼠则全部死亡。

在白鼬实验中进行几种就绪-加强混合物测试时，研究者看到了类似结果。白鼬被认为是预测流感疫苗人类反应的一种好的动物模型。接受一种DNA就绪-季节性加强疫苗的全部四只白鼬在2007病毒毒株的感染攻击下安然无恙，接受DNA就绪-感冒病毒加强混合物的全部6只白鼬则平安渡过1934流感病毒的攻击。

1 z6 O1 R' f6 q9 Z! _! @这些研究中的合作者包括疾病控制与预防中心的哲学博士Terrence Tumpey。

' Z8 {7 J9 r  P  x5 \3 v) F“我们对这些结果感到兴奋。该就绪-加强方法为流感接种打开了一扇新的大门， 这种接种跟对抗诸如肝炎的接种类似。因为对抗肝炎时是早年接种、然后通过在成年时偶尔、追加的预防接种来达到目的。”Nabel博士介绍说。
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: w$ |; Y( o0 U% u. ?Nabel博士又补充说：评估就绪-加强流感疫苗的安全性与能力的试验正在人类中进行。他说，在选择候选疫苗进一步作大型实验方面，来自该新研究的信息很有价值，“我们可能在三到五年内开始一种具有广泛保护能力的流感疫苗的效力试验。”