Scientists Frustrated in Search for Genital Herpes Vaccine

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Scientists Frustrated in Search for Genital Herpes Vaccine


科学家们对寻找生殖器疱疹疫苗感到灰心

By E.J. Mundell
HealthDay Reporter

FRIDAY, April 13 (HealthDay News) -- Experts say a lack of funds is slowing attempts to find a truly effective vaccine against genital herpes, a sexually transmitted disease that can be devastating for the one in five Americans over 12 who carry the virus.
4月13日，星期五（每日健康新闻）－专家们称资金的缺乏正在减缓寻找真正有效的生殖器疱疹疫苗的步伐。生殖器疱疹是一种性传播疾病，能祸及1/5的12岁以上携带这种病毒的美国人。
Genital infection with the herpes simplex viruses (HSV) 1 or 2 is not just an inconvenience, doctors note. It is a painful, recurrent illness that causes psychological distress, raises health risks for newborns, and boosts the carrier's odds for a much more deadly virus, HIV.
医生们称单纯疱疹病毒(HSV)1或2的生殖器感染带来的不仅仅是不便。它是一种令人痛苦的，可复发性疾病，能带来心理痛苦，增加新生儿健康风险，使携带者易于感染另一种致死性更强的病毒HIV。
And even as the Herpevac trial -- the first major publicly funded trial of a preventive vaccine -- is set to get under way, a leader of that trial says the vaccine, even if successful, would not be the solution to the herpes epidemic.
Herpevac试验的一位领导者称，即使目前正在进行的Herpevac试验（第一个重大的投资于保护性疫苗的公共资助性试验）研制成功，研制出的疫苗也不能解决疱疹的流行。
\"The Herpevac trial is a vaccine that is only going to affect the [uninfected] adolescent woman,\" said Dr. Lawrence Corey, head of infectious diseases and virology at the University of Washington, in Seattle. \"It is not going to be effective in men or in those who are HIV-positive. We need to do better.\"
Lawrence Corey是华盛顿大学传染病与病毒学主任，在西雅图称：“Herpevac试验所研制的疫苗，只对未感染HSV的成年女性起作用，对男性或HIV阳性个体无效。（因此）我们需要做得更好。”
Prior, expensive failures have made the drug industry skittish about funding herpes vaccine trials, however. So, despite the fact that most adult Americans either have HSV-1 or 2, or are at very high risk of contracting it in their lifetime, not enough is being done to stop the pathogen.
但是，先前昂贵的（试验）失败已使制药业对资助疱疹疫苗试验感到很恼火。所以，虽然多数美国人感染了HSV-1、2，或在日常生活中接触HSV的风险很高，但是目前的工作不足以阻止此病原体（的感染）。
\"I would say that, at the moment, the genital herpes vaccine is a field that does not have much interest, does not have much money,\" Corey said. \"The need for an HSV vaccine is really substantive, but there is not much of a program in the industrialized, developing world to develop such a vaccine.\"
Corey说：“我认为目前人们对生殖器疱疹领域关心的不够，资金投入的不多。HSV疫苗需求量很大，但在发达国家和发展中国家甚至都没有一个研制这种疫苗的计划。”
Part of the problem lies in the complexity of the virus. While simpler viruses such as the flu simply mutate their outer coats to evade the human immune system, HSV and other persistent viral infections are much more stable.
（导致）这一问题的部分原因是这种病毒的复杂性。虽然简单的病毒如流感病毒仅靠外壳突变就可以侵入人类免疫系统，但是（与之相比），HSV和其它持续性感染的病毒要稳定的多。
However, they have another secret weapon. Compared to other viruses, HSV 1 and 2 \"have a lot more genes and gene products that are redirecting and subverting the [host] immune response,\" Corey explained.
然而，它们拥有另一秘密武器。Corey解释说，与其它病毒相比，HSV-1、2拥有更多的基因和基因产物，可以改变和破坏宿主的免疫反应。
Although the two strains are similar and can infect either mouth or genitalia, HSV-1 is the prime cause of oral herpes (cold sores and fever blisters), while HSV-2 is the usual source of genital infections.
虽然HSV-1、2这两株病毒相似，都可以感染口和生殖器，但是HSV-1主要导致口的疱疹（感冒疮和热病性疱疹），HSV-2主要导致生殖器的感染。
Another tactic keeps herpes well-shielded from immune attack. Unlike pathogens that spread in readily accessed blood, HSV hides out in nerve cells called dorsal ganglia, located in the back. Specific triggers, such as sun exposure or stress, can send the virus traveling through nerve pathways to mucosal sites of activity in the genitalia, mouth and even eyes.
疱疹病毒还有另外一种方法可以很好地逃避免疫攻击。与易于通过血液传播的病原体不同，HSV隐藏于背部被称为脊髓神经节的神经细胞内。特异性激发因素，如日晒或压力，能够使病毒穿越神经通路到达生殖器、口甚至眼睛的粘膜活跃部位。
These nerve cells are \"a protected site, immunologically,\" explained Dr. Lawrence Stanberry, director of the Sealy Center for Vaccine Development at the University of Texas Medical Branch in Galveston. \"Needless to say, we don't like to have our immune system attacking our nerves,\" he said, so vaccines with that kind of reach are hard to develop.
Lawrence Stanberry是得克萨斯州医科大学加尔维斯顿分院Sealy中心疫苗研制主任，他解释说：这些神经细胞是免疫隔离部位。他说：“毫无疑问，我们不希望我们的免疫系统攻击自身的神经细胞，所以针对那个部位的疫苗很难研制。”
And yet, progress is being made. The Herpevac trial, funded by the U.S. National Institutes of Health and drug maker GlaxoSmithKline, is focused on a preventive vaccine aimed solely at uninfected women. Preliminary, phase III studies completed last year found the vaccine to be 73 percent effective in shielding young women from infection after exposure to HSV-2.
但是，（疫苗研制）计划正在制定中。美国国家健康协会与药物制造商GlaxoSmithKline资助的Herpevac试验，正在研制一种保护性疫苗，目标人群是未感染HSV的女性。去年已完成的第三阶段的初步研究发现，这种疫苗对保护年轻女性免于感染HSV-2的有效率为73％。
A 73 percent effectiveness rate may not sound all that impressive, but Stanberry -- also an investigator on the Herpevac trial -- said no one is expecting 100 percent immunization.
73％的有效率给人留下的印象不那么深刻，但是Herpevac试验的另一名研究者Stanberry说，没有人期望（疫苗）能做到100％的免疫。
\"What one hopes for with a vaccine is that you get very high rates of effectiveness and then very broad uptake of the vaccine [in the population],\" he explained. \"So then, if almost everyone gets immunized, then the disease simply doesn't circulate in the population to the same extent.\"
他解释说：“对于一种疫苗，人们期望的是有效率高，然后是人群中适应面广。所以，如果几乎所有人都接种疫苗，那么疾病在人群中的流行程度就不会是现在的程度。”
Reducing the \"pool\" of available virus will be vital to lowering the infection rate, researchers say, because the Herpevac shot does not protect uninfected men and cannot eliminate HSV from people who are already infected.
由于Herpevac不能保护未感染HSV的男性，不能清除已感染个体体内的病毒，所以研究者称，减少具有传染性的病毒库对于降低传染率至关重要。
The Herpevac trial is currently wrapping up recruitment of 7,000 healthy, HSV-negative U.S. women between the ages of 18 and 30. Participants will receive either the vaccine or a placebo and then be followed for 18 months to see if they become infected.
Herpevac目前已经募集了7000名健康的，HSV阴性的美国女性，其年龄范围为18到30岁。参与者将接种疫苗或安慰剂，然后在18个月后观察是否感染了HSV。
Stanberry said final results from the trial should be available by 2009, and -- if the vaccine proves effective -- a shot might be approved by 2010.
Stanberry说到2009年将拿到试验的最终结果，（如果证明疫苗有效）到2010年将可能会被批准。
However, like most modern vaccine trials, the Herpevac trial relies on a piece or \"subunit\" of HSV to prime the human immune system against incoming virus.
然而，Herpevac试验与多数现代疫苗试验相似，依赖HSV的一部分或 “亚单位”预致敏人类免疫系统以抵御病毒的入侵。
Another researcher is advocating the use of the live -- but greatly weakened -- form of the virus, instead.
与之相反，另一研究者主张使用活（毒性极大削弱的）病毒。
The problem with the subunit approach is that its effects don't last, said William Halford, a virologist at Montana State University, in Bozeman. \"Once you deliver it into someone's body, it's there, but, in a few weeks, it is gone,\" he said.
蒙大纳州大学病毒学家Halford在Bozeman称，使用亚单位法的问题是效力不能持久。他说：“一旦你将其注入某人身体，它就会呆在那里。但是几周过后，它就消失了。”
Live virus vaccines have a long and effective history. In fact, one of the few effective vaccines against any herpes strain -- the chickenpox/shingles (herpes zoster) shot -- was developed from live virus back in the 1960s.
活病毒疫苗有效时间长。事实上，少数几种针对任一疱疹株有效的疫苗（水痘/带状疱疹疫苗）是十九世纪六十年代由活病毒衍化而来。
Since that time, doctors have gotten more skittish about injecting people with a live form of the virus, however, so the subunit approach took precedence.
然而从那时起，医生们就对给人体注射活病毒十分恼火，，所以优先考虑亚单位法。
But Halford believes it is time to revisit the idea of a live virus herpes vaccine.
但Halford相信现在是重提活的疱疹病毒疫苗的时候了。
\"All we really have to do is to figure out a way to take away some of the genes or proteins that the virus needs to cause actual disease,\" he said. In other words, people would be infected with a very weak form of HSV, one that is sufficient to trigger a sustained immune response but too frail to trigger disease outbreaks.
他说“我们真正要做的是想方设法清除病毒赖以致病的一些基因或蛋白。”即人们需要感染一种致病力弱的HSV，这种病毒足以激发持久的免疫反应，但又不足以致病。
Halford is specifically investigating a protein in HSV called ICP0. \"If I take away the gene that codes for that protein, the virus is really weakened,\" he said.
Halford专门研究HSV中的一种称为ICP0的蛋白。他说：“如果我去除编码这种蛋白的基因，病毒的致病力的确会被削弱。”
The approach is controversial, but Corey believes it could have promise. \"I certainly think that the live attenuated virus is a viable approach to talk about,\" he said.
这种方法存在争议，但Corey相信它能实现。他说：“我确实认为（使用）这种致病力削弱的病毒的活性形式是一种可以探讨的方法”
Funding will be the real challenge, however, whatever the vaccine strategy. According to Corey, a series of expensive failures over the past two decades has dampened the enthusiasm of industry to invest in HSV vaccine research.
但是，无论采用什么方法研制疫苗，真正的挑战是资金的来源。Corey说，过去二十年中一系列昂贵的试验失败挫伤了制药业投资HSV疫苗研究的积极性。
\"I can give my own scenario in which we worked with [drug maker] Chiron and spent seven years and a lot of money -- decapitalizing the company by 25 percent -- on an antibody-based vaccine,\" Corey said. \"At the time, we thought it would be sufficient to work, but it didn't.\"
Corey说：“我可以举出我自己的实例。我们与制药商Chiron合作，用了7年，花了一大笔钱（用掉了公司25％的资金）研究抗体性的疫苗。目前，我们认为疫苗应该足够有效，但它却是无效的。”
So, with the private sector waiting on the sidelines, public funding becomes key.
所以，由于私人部门不参与使得公共投资变得很重要。
\"I think there needs to be more money from the publicly funded institutions -- whether they be foundations, the NIH or the National Research Council, in vaccine development,\" Corey said.
Corey说：“我认为疫苗的研制需要更多地来自公共投资机构的投资，不管是基金，NIH还是国家研究委员会。”
\"We also need to do more in defining a real path of success for a genital herpes vaccine,\" he added. \"Once some pathway of success becomes defined, then you'll see the pharmaceutical companies move forward.\"
他补充说：“我们同样需要更加努力，以找到一种真正有效的方法研制出生殖器疱疹疫苗。一旦找到了某一种有效的方法，你会看到药物公司很快就会跟进。”