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 25, 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. We are currently participating in an extension phase follow up of the individuals who received the vaccine under the main study, to accrue additional information on the persistence of vaccine efficacy.

Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2010
Total Cost
$106,763
Indirect Cost
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State
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Morrison, Vicki A; Johnson, Gary R; Schmader, Kenneth E et al. (2015) Long-term persistence of zoster vaccine efficacy. Clin Infect Dis 60:900-9
Morrison, Vicki A; Oxman, Michael N; Levin, Myron J et al. (2013) Safety of zoster vaccine in elderly adults following documented herpes zoster. J Infect Dis 208:559-63
Schmader, K E; Oxman, M N; Levin, M J et al. (2012) Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Clin Infect Dis 55:1320-8
Simberkoff, Michael S; Arbeit, Robert D; Johnson, Gary R et al. (2010) Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial. Ann Intern Med 152:545-54
Harbecke, Ruth; Oxman, Michael N; Arnold, Beth A et al. (2009) A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol 81:1310-22
Weinberg, Adriana; Zhang, Jane H; Oxman, Michael N et al. (2009) Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine. J Infect Dis 200:1068-77
Oxman, Michael N; Levin, Myron J; Shingles Prevention Study Group (2008) Vaccination against Herpes Zoster and Postherpetic Neuralgia. J Infect Dis 197 Suppl 2:S228-36