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HIV試驗疫苗增加感染可能

Trial Vaccine Made Some More Vulnerable to H.I.V., Study Confirms
HIV試驗疫苗增加感染可能

A follow-up study on an AIDS vaccine trial that had to be stopped early has confirmed the worst fears of researchers: The vaccine made it more likely, not less, that some men would become infected with H.I.V.

一項針對早前被迫終止的艾滋疫苗試驗的后續研究證實了研究者們最大的恐懼:該疫苗增大而不是減小了一些男性感染艾滋病病毒的可能性。

Men who were not circumcised and who had previously caught common colds caused by the same virus used to make the vaccine were two to four times as likely as other men to become infected if they got the vaccine, the study concluded.

研究得出結論:沒有接受過包皮環切的男性,以及曾感染過同種病毒(即用于研制疫苗的病毒)引起的普通感冒的男性,他們在接受疫苗之后感染艾滋病毒的可能性是其他男性的兩到四倍。
 

The new study shed no new light on how that happened. “I really wish I could tell you why, but I can’t,” said Dr. Ann Duerr, a vaccine specialist at the Fred Hutchinson Cancer Research Center in Seattle, who led the data analysis for the new study.

但新研究并沒有找到這一現象的原因。“我真的希望我能告訴你原因,但是我不能。”安·杜爾博士(Dr. Ann Duerr)說。他是位于西雅圖的弗雷德·哈欽森癌癥研究中心(Fred Hutchinson Cancer Research)的疫苗專家,主持此項新研究中的數據分析工作。

The trial of the Merck vaccine, which involved 3,000 volunteers in nine countries, began in 2004 and was abruptly halted in late 2007 when it became clear that it was not protecting anyone and suspicions arose that it was making some men more susceptible.

默克公司(Merck)研發的這一疫苗的試驗共有來自九個國家的3000名志愿者參與。試驗于2004年開始,但在2007年后期被突然停止,因為人們發現該疫苗不具有保護效果,并且懷疑它會致使某些男性更易受感染。

It was a frustrating failure and had repercussions across the AIDS vaccine field. Nine months later, government investigators canceled a trial of a similar vaccine because they were not sure why Merck’s had failed.

這項試驗的失敗讓人沮喪,對整個艾滋疫苗領域都造成了影響。九個月后,政府調查員叫停了另一項類似的疫苗試驗,因為他們不清楚默克疫苗失敗的原因。

The search for an AIDS vaccine has proceeded slowly and cautiously since then. The only success in the field — and there are many skeptics who doubt even the weak success that was proclaimed — came in 2009. A vaccine called RV 144 that was tested on 16,000 Thai volunteers seemed to lower, at least temporarily, a man’s chances of getting infected with H.I.V. by about 31 percent. But why that one worked, albeit badly, has remained a mystery.

從那以后,艾滋疫苗的研究進程緩慢而謹慎。唯一的一次成功是在2009年,盡管這一微小成功也引起了很多懷疑者的質疑。由16000名泰國志愿者參與的試驗表明,一種名為RV144的疫苗似乎能夠把感染艾滋病毒的幾率降低大約31%(至少是短期內)。但是疫苗成功的原因——即使效果不好——依然是一個迷。

The new study, published online this month in The Journal of Infectious Disease, followed 1,836 men from the Merck trial through the end of 2009. (More than a third of those who got the vaccine were women, but so few of them became infected that data about them was ignored.)

新研究發表在本月(5月,編者注)的《傳染病雜志》網絡版上。該研究跟蹤觀察了參與默克試驗的1836名男性,一直持續到2009年底。(有三分之一以上的受試者為女性,但她們少有人感染上艾滋病毒,故相關數據被省略。)

Of those men, 172 ultimately became infected. Uncircumcised men were more likely to get infected, as were men who began the trial with high levels of antibodies to Type 5 adenovirus -- one of hundreds of viruses that can cause sniffles and headache -- before they got the vaccine.

在受試的男性當中,有172人最終感染上了艾滋病毒。沒有接受包皮環切的男性,以及在注射疫苗前體內5型腺病毒抗體水平較高的男性均更容易被感染。5型腺病毒可以引起鼻塞和頭痛,類似的病毒有上百種。

But that increased vulnerability seemed to fade after 18 months.

但是,這種易感狀態似乎在18個月后逐漸消失。

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, a partner in the vaccine trial, said Dr. Duerr’s results “add credence to the belief that the effect was real” and the most likely explanation was a biological one.

美國國家過敏癥和傳染病研究所(National Institute of Allergy and Infectious Diseases)所長,同樣也是疫苗試驗合作人的安東尼·S·福奇博士(Dr. Anthony S. Fauci)說,杜爾博士的研究結果“給疫苗效果的真實性增加了可信度”,他還說,最有可能的解釋是從生理角度進行解釋。

The men did not engage in riskier behavior, like more partners, more drug injection or more unprotected sex, even after they were told whether they had been given the vaccine or the placebo, Dr. Duerr said.

杜爾博士說,即使是在獲悉自己接受的是疫苗還是空安慰劑之后,這些男性也沒有從事更危險的行為,像更多性伴、頻繁注射毒品或更多不安全性行為等。

That suggests that biology, rather than behavior, was to blame.

這說明易感狀態應該歸咎于生理,而不是行為。

The vaccine was made from a weakened adenovirus 5 modified to contain three genes — known as gag, pol and nef — that are found on the AIDS virus.

疫苗的來源是減毒5型腺病毒,該病毒經過改性后帶有三種基因— gag, pol 和 nef—這三種基因都可以在艾滋病毒上找到。

In theory, Dr. Duerr said, men who had already caught an adenovirus — and therefore had both antibodies to it and a set of CD4 cells, a kind of white blood cells, primed to recognize those antibodies — may have had their immune systems “boosted” by getting three shots of the same adenovirus. There may have been more CD4 cells present in their blood.

杜爾博士說,理論上,曾經感染過腺病毒的男性體內會生成相應抗體和一組CD4細胞(一種白細胞,功能是識別這些抗體)。這類男性在被注射三次相同病毒之后,其免疫系統大大增強。他們的血液里可能存在更多的CD4細胞。

Normally, more CD4s is a good response to a vaccine, but CD4s are exactly what H.I.V. attacks, so the vaccine could have been creating what the military calls a “target-rich environment.”

通常來說,更多的CD4細胞是接受疫苗后反應良好的表現,但是艾滋病毒的攻擊對象正好是CD4細胞,所以疫苗反而可能會創造出軍事上所說的“多目標作戰環境”。

Moreover, the underside of the penile foreskin is rich in Langerhans cells, which “grab” invading viruses and “present” them to CD4s as the immune system’s initial response.

另外,男性陰莖包皮的下面有很多朗格漢斯細胞,此種細胞可以“抓住”前來進攻的病毒并把它們“呈送”給CD4細胞,這是免疫系統的初始反應。

An adenovirus vector was chosen because these viruses have been shown to create strong immune responses. But because of what happened in 2007, both uncircumcised men and men with previous adenovirus infections have been excluded from the only large AIDS vaccine trial now under way; it is enrolling men in 16 American cities, according to Mitchell Warren, executive director of AVAC, a prevention advocacy group.

選擇腺病毒載體是因為腺病毒被發現可以引起強烈的免疫應答。因為2007年試驗叫停, 于是未割包皮的男性和曾經感染過腺病毒的男性都被排除出了目前唯一一個正在進行中的大型艾滋疫苗試驗。艾滋病疫苗推廣聯盟(AVAC)的執行主任米切爾.沃倫(Mitchell Warren)說,該試驗目前正在美國16個城市招收受試者。

There are dozens of adenoviruses, and researchers are now exploring rarer ones, including a chimpanzee adenovirus, to see if they might be usable in a vaccine, Mr. Warren added.

腺病毒共有幾十種,研究者們目前正在探索那些較為罕見的種類,包括黑猩猩腺病毒,以確定這些種類能否用于疫苗。沃倫先生補充說。

“The lesson,” Dr. Fauci said, “is that you’ve got to be careful if you use a vector vaccine.”

“疫苗試驗給我們的教訓就是:使用載體疫苗需要非常小心。” 福奇博士說。
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