[转移帖]HIV疫苗带来新风险

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原帖由论坛会员zhangning发表于 2007-12-7 17:15

HIV疫苗带来新风险

An HIV vaccine made by Merck that failed in clinical trials may have increased the susceptibility of some trial participants to the AIDS virus, researchers reported last week. The findings have left scientists grappling with the problem of how to handle future trials of vaccines that use similar strategies to stimulate an immune response.

研究人员上周说，莫克公司HIV疫苗临床实验的失败，也许会增加参与实验人群对AIDS的易感性。这项发现对于那些计划运用相似策略刺激免疫反应的科学家们，就未来如何设计疫苗实验进行争论。

The trial was suspended in September, when preliminary analyses showed that the vaccine failed to protect participants against HIV (see Nature  449, 390 ; 2007). The vaccine consisted of three HIV genes carried by a weakened viral vector. Neither the HIV genes nor the vector, made from a common-cold virus called adenovirus 5, were capable of causing infection.

该实验在9月份就已告停，初步分析显示疫苗对于实验人群没有保护作用(参见 Nature  449, 390 ; 2007)。该疫苗有三个HIV基因组成，并由一个减毒载体运载，都来源于称作腺病毒5的普通感冒病毒。不论是HIV基因还是载体都没能发生作用。

But it seems that trial participants who had a pre-existing immunity to adenovirus 5 were more likely to become HIV-positive if they received the vaccine. Among male volunteers who had high levels of antibodies against the adenovirus, 21 of 392 became infected in the vaccinated group, but only 9 of 386 were infected in the placebo group. The vaccine did not affect infection rates in men with no adenovirus-5 immunity.

但实验人群中曾对腺病毒5感染有过免疫反应的人群在注射疫苗之后，似乎更容易转变成HIV阳性。在男性自愿者中，发现了高水平的腺病毒抗体，392个接受疫苗的人中，21个感染，而对照组中386个人中只有9个感染。疫苗对于没有过腺病毒5免疫反应的人没有影响感染状况。

The trial was not designed to examine the relationship between adenovirus-5 immunity and HIV infection, and researchers cannot say whether the result is statistically significant. But they can't ignore the findings, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. The start of another HIV-vaccine trial has been pushed back several months to allow more time for scientific review, he says.

实验不是为检查腺病毒和HIV感染之间关系而设计的，研究人员对于实验结果是否有意义还不置可否。但他们不能忽略这个发现，位于马里兰州毕士大的美国过敏和传染病国家研究所主任Anthony Fauci说道，另一个HIV疫苗实验已经被推后数月施行，以留出更多的时间进行科学总结分析。

For now, researchers are trying to determine whether the vector is to blame or whether those with high adenovirus-5 immunity are at risk for unrelated reasons. Immunologists say it is also theoretically possible that vaccination in those with pre-existing immunity may have triggered an immune response that transiently boosted production of activated CD4 cells — the very immune cells that HIV infects.

现在，科研人员正试图寻找，到底是因为载体的原因，还是因为那些高水平腺病毒5的免疫反应对于不相干疾病的治疗有害。免疫学家说，在理论上，先前有过免疫反应的人在接受到同类刺激时，能迅速触发免疫系统做出反应，引发大量活性CD4细胞产生，而CD4正是HIV 感染的免疫细胞。

That theory leaves several questions unanswered. For example, it is not known how long after vaccination the activated CD4 cells would have remained in the mucosal surfaces where HIV first gains entry, says Fauci.

Fauci说，这个理论留下了许多未能解答的问题，例如，接种之后多久时间里，CD4细胞仍然留在HIV首次入侵的黏膜表面。

Researchers are nevertheless concerned. One possible solution is to limit future trials of adenovirus-5-based vaccines to participants with very low levels of immunity to the vector, says Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health in Bethesda, Maryland. But doing so would close off the trials to a large proportion of the population they aim one day to help: more than 80% of sub-Saharan Africans have significant levels of adenovirus-5 immunity. In addition to the planned HIV-vaccine trial, an Ebola vaccine in development also relies on an adenovirus-5 vector.

然而，研究人员倍受关注。未来实验中一个可能的解决办法，就是针对那些对载体有极低水平免疫反应的实验人群，限制使用基于腺病毒5的疫苗。位于马里兰州毕士大国家研究所的疫苗研究中心主任Gary Nabel说道。但如此做法，也许无法帮助大多数需要帮助的人群：南非有80%人群遭受严重的腺病毒感染。此外，对于那些即将进行临床实验的HIV疫苗，进展中的埃博拉病毒疫苗也用的腺病毒5载体。

But at this stage in vaccine development, researchers are just looking for a proof of concept rather than a vaccine that can be put directly to use, says Lawrence Corey, lead investigator of the HIV Vaccine Trials Network. Alternatives to adenovirus 5 are being developed, and may be substituted once the efficacy of a vaccination strategy has been shown. Nevertheless, vaccine developers will face challenging decisions in light of the new data, he says: “Translating uncertain data into policy is always a difficult issue.”

但在疫苗开发的这个阶段，研究人员只是期望找到支持理论的证据，而非直接能应用的疫苗，HIV疫苗实验网络第一调查人 Lawrence Corey说道。腺病毒5的谨慎使用已被提出，而且一旦接种策略被证明有效的话，就可能取代腺病毒5了。然而，疫苗开发人员将面临挑战性决策，因为可供参考的资料有限，他说到：”把未凿的资料转变为策略本身就是一个困难的问题。