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: 6). 03/2008; 197(6):825-35. DOI: 10.1086/528696
Source: PubMed


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.

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    • "ed by the parameter set ) after wards , as a modified interpretation of the Figure 8 . continued on next page Ogunjimi et al . eLife 2015 ; 4 : e07116 . DOI : 10 . 7554 / eLife . 07116 12 of 17 Research article Epidemiology and global health | Microbiology and infectious disease 2 . Exponential decrease from peak to 60% of pre - boosting value ( [ Levin et al . , 2008 ] , based on simulation from peak to year 1 , cf . supra ) , followed by a constant value for x years with x defined by the parameter set , but ≥3 years . After x years , VZV - CMI returns to the pre - boosting value . This scenario is compatible with the assumption that memory cells have a predefined and fixed lifespan as implied by We"
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    ABSTRACT: Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed.
    Full-text · Article · Aug 2015 · eLife Sciences
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    • "The IFN-␥ ELISPOT was used in two previous studies in older populations (≥60 years) [49] [55]. In one of these studies, the estimated GMFR was 2.1 at 6-weeks post-vaccination and 2.7 and 2.1 at 2 and 6-weeks post-vaccination, respectively, in the other study [49] [55]. "
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    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.
    Full-text · Article · Dec 2014 · Vaccine
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    • "In VZV specific immune response measurement performed on partial subjects out of subjects of SPS, immune reactions increased in vaccine inoculation group than placebo group in all three analysis methods such as glycoprotein enzyme-linked immunosorbent assay, responder cell frequency (RCF), and interferon-r enzyme-linked immune-sorbent spot-forming cell (IFN-r ELISPOT), and it was confirmed that the increase of immune reaction had negative correlation with the incidence of herpes zoster [14]. The preventive effect against herpes zoster was gradually decreasing during the first year of vaccine inoculation but they were maintained stably for at least three years, and PHN showed similar aspects. "
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    ABSTRACT: Herpes zoster and post-herpetic neuralgia deteriorate the quality of life because of severe pain and complications, and cause considerable social and economic burden of disease. In 2012, herpes zoster vaccine was released in Korea. The efficacy of herpes zoster vaccine is known to be 51.3-66.5% among the aged over 60 and 69.8-72.4% among adults between 50 and 59. It is also known that preventive efficacy is maintained for at least 5 years. Although there can be local reactions such as redness, pain and swelling at the site of injection and systemic reaction such as headache and eruption after herpes zoster vaccination, most of the adverse reactions are minor and disappear within days by themselves. As it is a live vaccine, persons with severe immune-suppression and pregnant women should not be vaccinated with the vaccine. Currently, Korean Society of Infectious Diseases recommended for the aged over 60 to be vaccinated with herpes zoster vaccine by subcutaneous route. In this article, clinical aspects and burden of disease of herpes zoster, efficacy and effects of herpes zoster vaccine, and herpes zoster vaccine recommendation by Korean Society of Infectious Diseases are discussed.
    Full-text · Article · Jul 2013
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