Trial Of Varicella Vaccine--Prevention Of Herpes Zoster

据估计，美国每年有60万至100万人感染带状疱疹。HZ的发病率和严重程度，以及其并发症的频率和严重程度，随着年龄的增长而显著增加。抗病毒治疗对HZ急性期影响不大。然而，它似乎不能预防带状疱疹后神经痛，这是HZ最常见的并发症。在过去的十年中，研究表明，与年龄相关的HZ发病率和严重程度的增加与与年龄相关的水痘-带状疱疹病毒(VZV)细胞免疫功能下降之间存在密切的时间关系。对老年人接种减毒水痘-带状疱疹活疫苗可显著和持久地提高VZV特异性细胞免疫。我们推测，通过增强VZV特异性细胞免疫反应，可以降低HZ及其并发症的发生率和严重程度。 这项名为带状疱疹预防研究(SPS)的重大临床研究由退伍军人事务部(VA)领导，并与NIAID和默克公司合作进行。这项全国性的试验在22个研究地点进行，历时5年半，共招募了38,546名志愿者。在这些人中，有1741人在NIH临床中心接种了疫苗。该疫苗将带状疱疹的发病率降低了51%：安慰剂组发生了642例带状疱疹，而接种疫苗组只有315例。在所有疫苗接受者中，带状疱疹引起的疼痛和不适的总负担比安慰剂接受者低61%。此外，与安慰剂相比，带状疱疹疫苗将带状疱疹后遗神经痛(PHN)的发生率降低了三分之二。PHN是一种慢性神经疼痛，是带状疱疹最常见的严重并发症。该疫苗耐受性良好，严重不良事件发生率低，接种地点的局部反应一般较轻。描述这一发现的手稿于2005年6月发表在《新英格兰医学杂志》上。默克公司向美国食品和药物管理局提交了带状疱疹疫苗的许可证申请。研究小组估计，如果获得批准使用，该疫苗可以预防每年在美国发生的25万例带状疱疹病例，并显著降低每年另外25万例带状疱疹病例的严重程度。 我们目前正在准备向接受安慰剂的参与者提供疫苗，并参与对个人的延长阶段跟踪，以获得有关疫苗效力持久性的更多信息。

Herpes Zoster (HZ) is estimated to affect between 600,000 to 1 million people annually in the United States. The incidence and severity of HZ, as well as the frequency and severity of its complications, increase markedly with age. Antiviral therapy has modest impact on the acute phase of HZ. However, it does not appear to prevent post herpetic neuralgia, the most common complication of HZ. During the past decade studies have revealed a close temporal relation between the age-related increase in the incidence and severity of HZ and an age-related decline in cell mediated immunity to varicella-zoster virus (VZV). The administration of a live attenuated varicella-zoster vaccine to older adults results in a marked and long lasting increase in VZV-specific cell-mediated immunity. We hypothesize that by boosting VZV-specific cellular immune responses, the incidence and severity of HZ and its complications can be reduced. Named the Shingles Prevention Study (SPS), this major clinical research study was led by the Department of Veterans Affairs (VA) and carried out in collaboration with NIAID and Merck & Co., Inc. This nationwide trial was conducted at 22 study sites over a 5 1/2-years period, and enrolled a total of 38,546 volunteers. Of these individuals, 1,741 were vaccinated at the NIH Clinical Center. The vaccine reduced the incidence of shingles by 51 percent: 642 cases of shingles occurred among those in the placebo group compared with only 315 in the vaccinated group. Among all vaccine recipients, the total burden of pain and discomfort due to shingles was 61 percent lower than in placebo recipients. Moreover, the zoster vaccine reduced the incidence of postherpetic neuralgia (PHN)--a form of chronic nerve pain that is the most common serious complication of shingles--by two-thirds compared with placebo. The vaccine was well tolerated, with the rates of serious adverse events low and local reactions at the vaccination site generally mild. A manuscript describing the findings was published at the New England Journal of Medicine in June 2005. Merck & Co., Inc submitted a license application to the Food and Drug Administration for the zoster vaccine. If approved for use, the research team estimates the vaccine could prevent 250,000 cases of shingles that occur in the United States each year and significantly reduce the severity of the disease in another 250,000 cases annually. We are currently preparing to offer the vaccine to the participants that received placebo, as well as participating in an extension phase follow up of the individuals to accrue additional information on the persistence of vaccine efficacy.