Trial Of Varicella Vaccine For The Prevention Of Herpes Zoster

据估计，美国每年有60万到100万人感染带状疱疹（HZ）。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，研究揭示了HZ发病率和严重程度的年龄相关性增加与水痘-带状疱疹病毒（VZV）细胞介导免疫力的年龄相关性下降之间的密切时间关系。老年人接种减毒水痘-带状疱疹活疫苗后，vzv特异性细胞介导的免疫力显著而持久地增强。我们假设通过增强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。

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 recently completed follow up on the extension substudy, which followed individuals who receive the vaccine under the initial study for an additional 5 years. This substudy enrolled 638 subjects. 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.