Trial Of Varicella Vaccine For The Prevention Of Herpes Zoster

据估计，带状疱疹（HZ）在美国每年影响60万至100万人。HZ的发生率和严重程度以及其并发症的频率和严重程度随年龄显著增加。抗病毒治疗对HZ急性期的影响不大。然而，它似乎不能预防带状疱疹最常见的并发症--带状疱疹后神经痛。在过去的十年中，研究已经揭示了与年龄相关的HZ的发病率和严重程度的增加和与年龄相关的水痘带状疱疹病毒（VZV）的细胞介导的免疫力下降之间的密切时间关系。对老年人接种水痘-带状疱疹减毒活疫苗可显著且持久地提高VZV特异性细胞介导的免疫力。我们假设通过增强VZV特异性细胞免疫应答，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）的主要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，Inc.这项全国性的试验在22个研究中心进行，为期5年半，共招募了38，546名志愿者。其中1,741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%：安慰剂组中有642例带状疱疹，而接种疫苗组只有315例。在所有疫苗接种者中，带状疱疹引起的疼痛和不适的总负担比安慰剂接种者低61%。此外，带状疱疹疫苗减少带状疱疹后神经痛（PHN）的发生率，PHN是一种慢性神经疼痛，是带状疱疹最常见的严重并发症，与安慰剂相比减少了三分之二。该疫苗耐受性良好，严重不良事件发生率低，接种部位的局部反应一般较轻。 2005年6月，一份描述这一发现的手稿发表在《新英格兰医学杂志》上。FDA于2006年5月26日批准ZOSTAVAX用于预防60岁及以上人群的带状疱疹，并于2006年10月26日由免疫实践咨询委员会（ACIP）推荐用于预防60岁及以上人群的带状疱疹。FDA于2011年3月24日批准ZOSTAVAX用于预防50岁及以上人群的带状疱疹。 我们已经完成了长期扩展子研究的随访，该研究对在初始研究中接种疫苗的个体进行了额外5年的随访。该子研究在NIH招募了638名受试者。该子研究的目的是在同一队列中积累有关ZOSTAVAX长期疗效的额外信息。正在对结果进行分析。

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 hypothesized 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. The FDA approved ZOSTAVAX for prevention of herpes zoster in individuals 60 years of age and older on May 26, 2006 and recommended by the Advisory Committee on Immunization Practices (ACIP) for people age 60 and older for prevention of herpes zoster in October 26, 2006. The FDA approved ZOSTAVAX for prevention of herpes zoster in individuals 50 years of age and older on March 24, 2011. We have completed follow up on the long term extension substudy, which followed individuals who receive the vaccine under the initial study for an additional 5 years. This substudy enrolled 638 subjects at NIH. The aim of this substudy is to accrue additional information on the long-term efficacy of ZOSTAVAX in this same cohort. Analyses of the results are being performed.