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【medical-news】HIV疫苗雪上加霜－－受试者HIV感染
HIV vaccine may raise risk
Infection rates increase in some trial participants.
Heidi Ledford
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.
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.
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.
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.
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.
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.
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.
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.” HIV vaccine may raise risk
HIV疫苗可能增加感染风险
Infection rates increase in some trial participants.
在部份受试者HIV的感染率增加
Heidi Ledford
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.
上周，Meck公司的HIV试验疫苗因为可能增加受试者感染风险而宣告失败。但研究者认为该研究还是为今后HIV疫苗的研究提供重要价值，该研究有助于将来如何避免此类问题发生，并能获得保护性免疫。
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.
试验于今年9月宣布暂停，当时初步报告显示不能为受试者提供保护。该疫苗是由一种普通感冒病毒腺病毒5携带3个HIV基因，而不论是HIV基因还是感冒病毒都没有感染能力。
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.
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作者:admin@医学,生命科学 2011-03-24 14:00
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