Article

Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine.

University of Colorado Health Sciences Center, Denver, Colorado, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 03/2008; 197(6):825-35. DOI: 10.1086/528696
Source: PubMed

ABSTRACT A double-blind, placebo-controlled trial that involved 38,546 subjects > or =60 years old demonstrated efficacy of a high-potency live-attenuated Oka/Merck varicella-zoster virus (VZV) vaccine. The trial included an immunology substudy to determine the relationship of VZV-specific immune responses to vaccination and clinical outcome.
The immunology substudy enrolled 1395 subjects at 2 sites where blood samples obtained prior to vaccination, at 6 weeks after vaccination, and at 1, 2, and 3 years thereafter were tested for VZV-specific cell-mediated immunity (VZV-CMI) by gamma-interferon ELISPOT and responder cell frequency assays and for VZV antibody by glycoprotein ELISA.
VZV-CMI and VZV antibodies were significantly increased in vaccine recipients at 6 weeks after vaccination. The vaccine-induced increases in VZV-CMI persisted during the 3 years of follow-up, although their magnitude decreased over time. The magnitude of these VZV-specific immune responses was greater in subjects 60-69 years old than in subjects > or =70 years old.
The zoster vaccine induced a significant increase in VZV-CMI and VZV antibody. The magnitude and duration of the boost in VZV-CMI in vaccine recipients and the relationship of this boost to age paralleled the clinical effects of the vaccine observed during the efficacy trial. These findings support the hypothesis that boosting VZV-CMI protects older adults against herpes zoster and postherpetic neuralgia.

Full-text

Available from: Michael R Irwin, Aug 25, 2014
0 Followers
 · 
162 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Zostavax® is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay and of the safety were secondary objectives.
    Vaccine 12/2014; 4(6). DOI:10.1016/j.vaccine.2014.12.024 · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary infection with varicella zoster virus (VZV) results in varicella (chickenpox) followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, shingles). HZ is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. There are currently two FDA-approved vaccines for the prevention of VZV: Varivax® (for varicella) and Zostavax® (for HZ). Both vaccines contain the live-attenuated Oka strain of VZV. Although highly immunogenic, a two-dose regimen is required to achieve a 99% seroconversion rate. Zostavax vaccination reduces the incidence of HZ by 51% within a 3-year period, but a significant reduction in vaccine-induced immunity is observed within the first year after vaccination. Developing more efficacious vaccines and therapeutics requires a better understanding of the host response to VZV. These studies have been hampered by the scarcity of animal models that recapitulate all aspects of VZV infections in humans. In this review, we describe different animal models of VZV infection as well as an alternative animal model that leverages the infection of Old World macaques with the highly related simian varicella virus (SVV) and discuss their contributions to our understanding of pathogenesis and immunity during VZV infection.
    06/2013; 2(2):364-382. DOI:10.3390/pathogens2020364
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vaccination programmes are implemented either as new vaccines become available or evidence about them accumulates, or in response to specific situations. In the United Kingdom, development and implementation of the national immunisation programme is centrally coordinated and funded by the Department of Health on behalf of England, Wales, Scotland and Northern Ireland. A number of significant changes were made to the UK immunisation schedule for 2013/2014. Three new vaccines were introduced: intranasal influenza and oral rotavirus for children and subcutaneous shingles for older adults. To ensure protection against meningococcal C infection into adulthood, there has been a change to the schedule for meningitis C vaccination. The temporary pertussis vaccination programme for pregnant women, set up in response to an increase in the number of cases of pertussis particularly among young babies, has been extended until further notice. Furthermore, in response to large outbreaks of measles in south Wales and other parts of the UK, a national measles, mumps and rubella catch-up campaign specifically targeted at unvaccinated children aged 10-16 years was launched to ensure that all children and young people have received two doses of measles, mumps and rubella vaccine. This review describes the rationale behind these policy changes.
    04/2015; 6(4):2054270415577762. DOI:10.1177/2054270415577762