????今年的流感疫情非常嚴(yán)峻。從去年秋天至今，已經(jīng)有數(shù)千美國(guó)人死于流感，其中包括56名兒童。美國(guó)疾病控制與預(yù)防中心已經(jīng)發(fā)布了流感預(yù)警，而現(xiàn)在我們才剛剛進(jìn)入二月，也就是流感疫情通常會(huì)集中爆發(fā)的月份。

????流感疫情如此嚴(yán)重的部分原因是，今年的流感疫苗注射效果是近十年來最弱的一次。這或許也可以解釋今年的流感疫情為什么如此早地就達(dá)到流行病級(jí)別。美國(guó)疾病控制與預(yù)防中心表示，今年的流感疫苗有效率只有23%，遠(yuǎn)低于往年50%到60%的水平。

????流感疫苗并不是一項(xiàng)高新技術(shù)，早在1935年，人類就測(cè)試了第一支流感疫苗。僅僅7年后，也就是1942年，美國(guó)就開始在美軍基地里進(jìn)行大規(guī)模的流感疫苗研究。那么經(jīng)過了70多年的研究，為什么我們還沒有創(chuàng)造出一種持續(xù)有效的流感疫苗呢？

????分析流感變種

????每年2月，世界衛(wèi)生組織都會(huì)召集全球流感專家進(jìn)行研討，以確定下一季流感疫苗所使用的病毒株。全球科學(xué)家和醫(yī)生都在努力收集和分析當(dāng)前流行的病毒株，希望找到那些有可能演化為新流感的病毒變種。

????美國(guó)疾病控制與預(yù)防中心的世衛(wèi)合作中心負(fù)責(zé)人杰基?卡茨表示：“這是一個(gè)持續(xù)不斷的過程。一個(gè)病毒的變種會(huì)衍生出一系列變種。它是一種持續(xù)不斷的線性進(jìn)化，但也是很難預(yù)測(cè)的。想獲得一支精確的流感疫苗，關(guān)鍵就在于及時(shí)獲得病毒樣本，這樣我們才能及時(shí)分析，準(zhǔn)備下一年的疫苗。”

????一旦這些病毒株被確定，專家就會(huì)針對(duì)其中的三到四種，來研制下一年的疫苗。這些病毒株會(huì)被大量生產(chǎn)，然后交給葛蘭素史克、諾華和賽諾菲等生產(chǎn)廠家來生產(chǎn)和銷售——這個(gè)過程需要顯著的提前期，才能保證疫苗在10月初到達(dá)各地的醫(yī)院。

????去年二月中旬開始的疫苗研制過程，也和往年沒有什么差別。來自美國(guó)疾病控制與預(yù)防中心、美國(guó)食品藥品監(jiān)督管理局(FDA)、美國(guó)國(guó)家衛(wèi)生研究院和世界衛(wèi)生組織和其他國(guó)際機(jī)構(gòu)的官員在瑞士日內(nèi)瓦召開會(huì)議，確定了下一年度可能在北半球流行的流感病毒株，然后將它們交給生產(chǎn)廠商。（為了給南半球研制流感疫苗，去年9月也召開了另一場(chǎng)類似的峰會(huì)。）

????到了去年三月，一種流感病毒的變種突然出現(xiàn)了，科學(xué)家們知道它有肆虐的可能，但為時(shí)已晚?？ù谋硎荆骸皶r(shí)間是我們研制流感疫苗最大的敵人?！?/p>

????疫苗是如何生產(chǎn)的

????據(jù)葛蘭素史克公司介紹，最普通的流感疫苗生產(chǎn)方法往往會(huì)使用雞蛋，這個(gè)過程會(huì)持續(xù)5個(gè)月。幾百萬只受精的雞蛋會(huì)被用作流感病毒的培養(yǎng)基，然后病毒會(huì)被收集、提純并裝進(jìn)藥瓶。在疫苗正式投放全國(guó)之前，生產(chǎn)廠家和FDA會(huì)測(cè)試它們的效能和安全性。

????這個(gè)方法從上世紀(jì)50年代就開始采用。這是一個(gè)緩慢且冗長(zhǎng)的過程，尤其是考慮到它面臨的挑戰(zhàn)。首先，生產(chǎn)過程依賴足夠的受精雞蛋。如果雞蛋的供給不足，那就會(huì)影響免疫血清的產(chǎn)量。其次，有些病毒變種在雞蛋里成長(zhǎng)得并不好，有的還會(huì)發(fā)生意想不到的變異，從而影響疫苗的效能。

????約翰霍普金斯大學(xué)布隆伯格公共衛(wèi)生學(xué)院教授安德魯?皮克茲表示：“問題的關(guān)鍵在于要改變疫苗的生產(chǎn)方式，它是制約疫苗精確性的一個(gè)重要因素。其實(shí)，我們確定這些病毒株的速度是非?？斓?，尤其考慮到它對(duì)細(xì)節(jié)的要求?！?/p>

????從2013年1月起，一種新的疫苗生產(chǎn)方式開始進(jìn)入市場(chǎng)。它的生產(chǎn)速度更快，不需要用雞蛋作為培養(yǎng)基，而且它的效能可能會(huì)更高。這種疫苗被稱作“重組蛋白疫苗”，它采用了一種流感病毒蛋白質(zhì)，這種蛋白質(zhì)是通過改變一種感染昆蟲細(xì)胞的病毒的基因而合成的。它可以引發(fā)人體的免疫反應(yīng)，生成保護(hù)性抗體。

????FluBlok是第一支也是首支獲得FDA認(rèn)證的重組蛋白疫苗。其制造商Protein Sciences公司的女發(fā)言人雷切爾?菲爾伯鮑姆指出：“生產(chǎn)出疫苗只需要幾個(gè)星期，而不是幾個(gè)月。另外它還含有三倍的抗原，能起到更好的保護(hù)效果。有了這項(xiàng)技術(shù)，我們基本上避免了時(shí)間上的拖延?！?/p>

????重組蛋白疫苗通常需要6到12周的生產(chǎn)時(shí)間。在發(fā)生流感大爆發(fā)的情況下，Protein Sciences只需要3到6個(gè)月的時(shí)間，就能向全美提供5000萬支流感疫苗。而用雞蛋培養(yǎng)的疫苗要想達(dá)到這樣的應(yīng)急產(chǎn)量，則至少需要6個(gè)月的時(shí)間。

????與時(shí)間賽跑

????重組技術(shù)通過基因手段在成長(zhǎng)速度更快的昆蟲細(xì)胞中孵化流感蛋白質(zhì)，從而可以為科學(xué)家節(jié)省更多寶貴的時(shí)間，更精確地確定下一季可能爆發(fā)的流感病毒變種。它必定能夠幫助科學(xué)家更好地研制今年的疫苗。

????皮克茲表示：“我們只需要花四五個(gè)星期的時(shí)間，就能信心十足地抓住即將流行的流感病毒變種的長(zhǎng)尾巴?！?/p>

????該技術(shù)有可能為我們節(jié)省寶貴的時(shí)間，但它仍是一項(xiàng)新技術(shù)。為了應(yīng)對(duì)今年的流感季節(jié)，葛蘭素史克公司生產(chǎn)了約2400萬支基于雞蛋培養(yǎng)基生產(chǎn)的流感疫苗，在美國(guó)還有其他四家公司也在使用雞蛋培養(yǎng)基技術(shù)。相比之下，Protein Sciences公司今年只推出了30萬支FluBlok流感疫苗。

????目前整個(gè)行業(yè)都在大力投資重組技術(shù)，其中也包括葛蘭素史克。不過菲爾伯鮑姆表示，大多數(shù)廠商在這項(xiàng)技術(shù)上都落后了10到15年。Protein Sciences計(jì)劃明年將FluBlok疫苗的產(chǎn)量提高到120萬支，不過對(duì)于美國(guó)總體的流感疫苗需求量來說，這還只是一個(gè)很小的比例。

????科學(xué)家的終極目標(biāo)是研制一種能夠治愈所有流感變種的疫苗。《財(cái)富》記者埃里卡?弗萊正在深入研究科學(xué)家們將如何在接下來的大約10年內(nèi)實(shí)現(xiàn)這個(gè)目標(biāo)。

????直到現(xiàn)在，全球科學(xué)家還在認(rèn)真準(zhǔn)備今年二月的流感峰會(huì)，他們希望在會(huì)上精確地確定明年的流感變種——這可能會(huì)拯救幾萬人的生命。

????皮克茲表示：“在大多數(shù)年份里，我們的匹配工作都做得很好，這也是我們能夠獲得進(jìn)展的情形之一，但這項(xiàng)工作需要各方齊心協(xié)力，不只是科學(xué)家，生產(chǎn)和監(jiān)管環(huán)節(jié)也必須及時(shí)跟上才行?！保ㄘ?cái)富中文網(wǎng)）

????譯者：樸成奎

????審校：任文科

????After 70 years, why aren’t we better at developing flu vaccines?

????This year’s influenza season is a serious one. Thousands of Americans — including 56 children — have died from the flu since last fall. The Centers for Disease Control and Prevention (CDC) has labeled the outbreak an epidemic, and we’re barely into February, the month that typically brings the peak of the season.

????Part of the problem is this year’s flu shot has been one of the least effective in a decade, and it may account for why we are seeing the flu reach epidemic levels so early this season. The current flu vaccine is only 23% effective, compared to between 50% and 60% efficacy for a typical seasonal flu vaccine, according to the CDC.

????The flu vaccine isn’t a newfangled technology. The first human influenza vaccines were tested as early as 1935, and extensive flu vaccine studies were started on U.S. army bases in 1942. So, after more than 70 years of research, why aren’t we better at creating a consistently effective seasonal flu vaccine?

????Analyzing the strains

????The answer to that question begins in February of every year, when global flu experts and the World Health Organization meet as part of an annual consortium to peg the influenza strains for the following season’s flu vaccine

????Scientists and doctors from around the world work diligently to collect and analyze the flu strains currently in circulation, looking to pinpoint mutations that could become ground zero for a new epidemic.

????“It’s a constant process,” said Jackie Katz, the head of the CDC’s WHO collaborating center. “One set of mutations will build on another. It’s a constant sort of linear evolution, but it’s one that is very hard to predict. One of the key features to get an accurate vaccine is having the viruses arrive in time, so we can characterize and analyze these viruses for the coming season.”

????Once those strains are identified, the experts choose three to four to include in the next season’s vaccine. Those strains are then produced and handed off to manufacturers, such as GlaxoSmithKline, Novartis and Sanofi, to produce and distribute — a process that requires significant lead time to ensure the doses reach doctor offices by early October.

????This same process happened in mid-February last year. Officials from the CDC, Food and Drug Administration, National Institute of Health, WHO, and other international bodies, met in Geneva, Switzerland, to pinpoint the strains that would be prevalent in the Northern Hemisphere then handed those off to manufacturers. (A separate but similar summit happens for the Southern Hemisphere in September.)

????The problem came in March when a mutation showed up that scientists knew would wreak havoc, but it was too late. “Time is one of our biggest enemies for the flu vaccine,” said Katz.

????How vaccines are made

????The most common vaccine production method useschicken eggs. This process takes about five months, according to GlaxoSmithKline. Millions of fertilized eggs are used as a culture to grow influenza viruses, which are then harvested, purified and packaged into vials. Manufacturers and the FDA then test for potency and safety before shipping the lot releases around the country.

????This method has been in practice since the 1950s. It’s slow and tedious, especially given the challenges. Firstly, manufacturing relies on the availability of enough fertilized eggs. If egg supplies were ever compromised it would affect our ability to produce enough serum. Second, some flu strains don’t grow that well in chicken eggs and undergo undesirable mutations that affect the potency of a seasonal vaccine.

????“The question is about changing the way these vaccines are made. It’s the real factor limiting the accuracy,” said Andrew Pekosz, a professor at Johns Hopkins University’s Bloomberg School of Public Health. “The speed at which we can identify these strains, especially given the level of detail, is very rapid.”

????As of January 2013, a new vaccine production method hit the market. It’s faster, egg-free and potentially more effective. It’s called a recombinant protein vaccine and uses an influenza virus protein that’s made by genetically altering a virus that infects insect cells. The resulting protein is what triggers the immune response in humans to make protective antibodies.

????“It takes only weeks versus months to produce,” said Rachel Felberbaum, a spokeswoman for Protein Sciences, the maker of FluBlok, the first and only FDA approved recombinant influenza vaccine. “It also has three times the antigens, which helps protect better. We can do that without a time lag because of the technology.”

????The recombinant vaccine typically takes between six to 12 weeks to manufacture, and in the case of a pandemic Protein Sciences is ready to provide 50 million doses to the U.S. government in as quickly as three to six months. Egg-based vaccines would require at least six months for similar emergency output.

????Vying for time

????Recombinant technology — which uses genetic modification to incubate the flu proteins in faster-growing insect cells — could help carve out the vital time that scientists need to more accurately target influenza strains that will circulate during the upcoming season. It certainly would have helped scientists better target this year’s vaccine.

????“All we need is to buy four to five weeks to have a high level confidence of catching the long tail of emerging variants,” said Pekosz.

????The technology has potential to buy that extra time, but it’s still new. For this year’s flu season, GlaxoSmithKline produced about 24 million vaccine doses using the egg-based method, and it is one of five companies producing traditional egg-based flu vaccines in the U.S. In comparison, Protein Sciences released 300,000 FluBlok doses this season.

????The industry as a whole is investing in this recombinant technology, including GlaxoSmithKline GSK -0.09% . However, most manufacturers are still about 10 to 15 years behind, said Felberbaum. Protein Sciences plans to scale up to 1.2 million FluBlok doses for the next flu season, though that’s still a small portion of the overall vaccine quantity needed for the U.S.

????Ultimately, scientists hope for a universal vaccine — one shot that would cure all influenza strains.Fortune’s Erika Fry delved into how scientists are working toward that end goal, which remains nearly 10 years off.

????Until then, scientists around the world are working diligently to be prepared for this February’s influenza summit when they hope to accurately pinpoint next season’s strains — potentially saving tens of thousands of lives.

????“In most years, we have a pretty good match,” said Pekosz. “It’s one of those situations where we could improve, but it takes a really concerted effort. It’s not just science, but manufacturing and regulations.”