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.
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.
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.
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.
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.
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.)
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.
But that increased vulnerability seemed to fade after 18 months.
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.
That suggests that biology, rather than behavior, was to blame.
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.
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.”
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.
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.
“The lesson,” Dr. Fauci said, “is that you’ve got to be careful if you use a vector vaccine.”